Pneumonia. Definition. Classification. Clinical pattern.Syndrome of pulmonary tissueconsolidation . Diagnostics. Treatment. Complications. Prognosis.

Lung cancer. Ethioliogy. Clinical pattern. Diagnostics. Treatment.

Pleurisy. Syndrome of liquid accumulation in pleural cavity. Ethioliogy. Clinical pattern. Diagnostics. Treatment.

 

PNEUMONIA

 

Pneumonia is an inflammatory condition of the lung—affecting primarily the microscopic air sacs known as alveoli It is usually caused by infection with viruses or bacteria.

The term pneumonia is sometimes more broadly applied to any condition resulting in inflammation of the lungs (caused for example by autoimmune diseases, chemical burns or drug reactions); however, this inflammation is more accurately referred to as pneumonitis.

Annually, pneumonia affects approximately 450 million people, seven percent of the world’s total, and results in about 4 million deaths. Although pneumonia was regarded by William Osler in the 19^th century as “the captain of the men of death”, the advent of antibiotic therapy and vaccines in the 20^th century has seen improvements in survival Nevertheless, in developing countries, and among the very old, the very young and the chronically ill, pneumonia remains a leading cause of death.

Aetiology and pathogenesis. All authors who studied the aetiology of lobar pneumonia (pleuropneumonia, croupous pneumonia), discovered Frenkel pneumococci (mostly types I and II, less frequently types III and IV) in about 95 per cent of cases. Fridlaender diplobacillus, Pfeiffer’s bacillus, streptococcus, staphylococcus, etc. are found less frequently.

Lobar pneumonia occurs mostly after severe overcooling. The main portal of infection is bronchogenic, less frequently lymphogenic and haematogenic. Congestion in the lungs in cardiac failure, chronic and acute diseases of the upper airways, avitaminosis, overstrain and other factors promote the onset of pneumonia. Acute lobar pneumonia is relatively frequent in patients who had pneumonia in their past history (it re 30—40 per cent of cases which is another evidence of the  character of the disease).

Pneumonia is primarily due to infections caused by bacteria or viruses and less commonly by fungi and parasites. Although there are more than 100 strains of infectious agents identified, only a few are responsible for the majority of the cases. Mixed infections with both viruses and bacteria may occur in up to 45% of infections in children and 15% of infections in adults.^[ causative agent may not be isolated in approximately half of cases despite careful testing.

Infective agents were historically divided into “typical” and “atypical” based on their presumed presentations, but the evidence has not supported this distinction, thus it is no longer emphasized.

Conditions and risk factors that predispose to pneumonia include: smoking, immunodeficiency, alcoholism, chronic obstructive pulmonary disease, chronic kidney disease, and liver disease. The use of acid-suppressing medications -such as proton-pump inhibitors or H2 blockers– is associated with an increased risk of pneumonia. Old age also predisposes pneumonia.

Bacteria

Bacteria are the most common cause of community-acquired pneumonia (CAP), with Streptococcus pneumoniae isolated iearly 50% of cases. Other commonly isolated bacteria include: Haemophilus influenzae in 20%, Chlamydophila pneumoniae in 13%, and Mycoplasma pneumoniae in 3% of cases; Staphylococcus aureus; Moraxella catarrhalis; Legionella pneumophila and Gram-negative bacilli. A number of drug-resistant versions of the above infections are becoming more common, including drug-resistant Streptococcus pneumoniae (DRSP) and methicillin-resistant Staphylococcus aureus (MRSA).

The spreading of organisms is facilitated when risk factors are present. Alcoholism is associated with Streptococcus pneumoniae, anaerobic organisms and Mycobacterium tuberculosis; smoking facilitates the effects of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Legionella pneumophila. Exposure to birds is associated with Chlamydia psittaci; farm animals with Coxiella burnetti; aspiration of stomach contents with anaerobic organisms; and cystic fibrosis with Pseudomonas aeruginosa and Staphylococcus aureus. Streptococcus pneumoniae is more common in the winter,[ and should be suspected in persons who aspirate a large amount anaerobic organisms.

 

Pneumococci are typically associated with pneumonia

 

Viruses

In adults, viruses account for approximately a third and in children for about 15% of pneumonia cases. Commonly implicated agents include: rhinoviruses, coronaviruses, influenza virus, respiratory syncytial virus (RSV), adenovirus, and parainfluenza. Herpes simplex virus rarely causes pneumonia, except in groups such as: newborns, persons with cancer, transplant recipients, and people who have significant burns. People following organ transplantation or those who are otherwise immunocompromised present high rates of cytomegalovirus pneumonia. Those with viral infections may be secondarily infected with the bacteria Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae, particularly when other health problems are present. Different viruses predominate at different periods of the year, for example during influenza season influenza may account for over half of all viral cases. Outbreaks of other viruses also occasionally occur, including hantaviruses and coronavirus.

Pathanatomy. There are four stages to pneumonia which an individual may go through after contracting the condition.  The first stage will involve the body actually accumulated bacteria. The infection will continue to grow as the number of bacteria increase. As a result, this will lead to the second stage of pneumonia which is also known as the red hepatisation stage. At this stage, the alveolar spaces in the lungs will start to become blocked with blood and this may even start appearing on the surface of the lungs. These air sacs or alveoli will start to become more and more inflamed as they become filled with fluid. At the third stage, the red blood cells will begin to break up and this is also known as the gray hepatization stage. The last stage occurs when fluids in the lungs are broken down by enzymes and this may also include pus.  The body’s natural reaction to trying to clear these fluids from the lungs is through coughing as it becomes more difficult for the individual to breathe. As the lungs are becoming more filled, there is less space for oxygen to be absorbed into the body and this could lead to further complications as the body is unable to transport as much oxygen rich blood to its major organs. For groups such as babies, young children, the elderly, smokers or those with a pre-existing lung condition or weakened immune system, hospital treatment may be necessary. For those with a milder form of pneumonia, it may be possible to treat the condition at home with a course of antibiotics.

Pathanatomic preparation of lung tissue in pneumonia in stage of red hepatisation (red colour) and abscesses (white colour)

 

Lung parenchyma in pneumonia in stage of grey hepatisation

 

Pathogenesis. Viruses may reach the lung by a number of different routes. Respiratory syncytial virus is typically contracted when people touch contaminated objects and then they touch their eyes or nose. Other viral infections occur when contaminated airborne droplets are inhaled through the mouth or nose. Once in the upper airway the viruses may make their way in the lungs, where they invade the cells lining the airways, alveoli, or lung parenchyma. Some viruses such as measles and herpes simplex may reach the lungs via the blood. The invasion of the lungs may lead to varying degrees of cell death. When the immune system responds to the infection, even more lung damage may occur. White blood cells, mainly mononuclear cells, primarily generate the inflammation. As well as damaging the lungs, many viruses simultaneously affect other organs and thus disrupt other body functions. Viruses also make the body more susceptible to bacterial infections; in this way bacterial pneumonia can arise as a co-morbid condition.

Bacterial

Most bacteria enter the lungs via small aspirations of organisms residing in the throat or nose. Half of normal people have these small aspirations during sleep. While the throat always contains bacteria, potentially infectious ones reside there only at certain times and under certain conditions. A minority of types of bacteria such as Mycobacterium tuberculosis and Legionella pneumophila reach the lungs via contaminated airborne droplets.Bacteria can spread also via the blood. Once in the lungs, bacteria may invade the spaces between cells and between alveoli, where the macrophages and neutrophils (defensive white blood cells) attempt to inactivate the bacteria. The neutrophils also release cytokines, causing a general activation of the immune system. This leads to the fever, chills, and fatigue common in bacterial pneumonia. The neutrophils, bacteria, and fluid from surrounding blood vessels fill the alveoli resulting in the consolidation seen on chest X-ray.

 

 

Classification of pneumonia:

Pneumonitis refers to lung inflammation; pneumonia refers to pneumonitis, usually due to infection but sometimes non-infectious, that has the additional feature of pulmonary consolidation. Pneumonia is most commonly classified by where or how it was acquired: community-acquired, aspiration, healthcare-associated, hospital-acquired, and ventilator-associated pneumonia. It may also be classified by the area of lung affected: lobar pneumonia, bronchial pneumonia and acute interstitial pneumonia; or by the causative organism. Pneumonia in children may additionally be classified based on signs and symptoms as non-severe, severe, or very severe.

 

Community-acquired pneumonias;

Pneumonia in immunocompromised host

Nosocomial pneumonia

Aspiration pneumonia

 

 

Community-acquired pneumonia has become a major health problem throughout the world. Each year in the United States, an estimated 4 million cases occur. About 20% of these cases require hospitalization, the condition resulting in more than 65 million days of restricted activity overall. Mortality rates range from 1% to 5% in death. Many experts divide therapy for community-acquired pneumonia into two categories: inpatient and outpatient.

Problems in establishing a cause The etiology of community-acquired pneumonia is a long- and often-debated topic. Some researchers imply that outpatients contract different causative agents than do inpatients, while other investigators do not make major distinctions between the two categories. Other experts have attempted to elucidate the causes according to patient age. Even after examination of virtually every study completed on community-acquired pneumonia, it is extremely difficult to posit any useful probability of cause on the basis of age or outpatient versus inpatient setting.

The difficulty arises from a simple fact: in most patients with community-acquired pneumonia (about 98% of those treated as outpatients and 50% to 60% of those treated as inpatients), the causative organism is not known. Even in studies at academic centers where every effort is made to culture samples from all conceivable sites, the success rate in determining a cause is only about 50%. In most cases with an “established” cause, testing has been done on expectorated sputum, and this source of sample material always has the potential of contamination with upper-airway organisms. Correlation is not high between findings in expectorated sputum and findings in specimens from lower in the respiratory tract, obtained by bronchoscopy with a protected brush or by fine-needle or transtracheal aspiration.

A variety of organisms can cause community-acquired pneumonia. A review of studies during the past 20 years that included more than 100 subjects (total, >4,900 patients) reveals that the following are the most common pathogens(1): Streptococcus pneumoniae (9% to 75%; mean, 33%), Haemophilus influenzae (0 to 50%; mean, 10%), Legionella species (0 to 50%; mean, 7%), and Chlamydia pneumoniae (0 to 20%; mean, 5%) (1,3,5,8). Other organisms reported, io particular order, were Mycoplasma pneumoniae, other gram-positive organisms, gram-negative organisms, anaerobes, mycobacteria, fungi, and viruses. The incidence of so-called “atypical” (legionellal, chlamydial, and mycoplasmal) pneumonias is particularly difficult to ascertain, because diagnosis of these infections is usually made by serologic testing. This method indicates only whether there has been exposure to these organisms and an immunologic response; it does not necessarily establish that they are causative agents of the pneumonia under scrutiny.

Despite all the contradictory statistics on etiology, most investigators agree that S pneumoniae is the leading cause of community-acquired pneumonia in both inpatients and outpatients.

 

Hospital-acquired pneumonia

Hospital-acquired pneumonia is an infection of the lungs that occurs during a hospital stay. This type of pneumonia can be very severe. Sometimes it can be fatal.

Causes

Pneumonia is a common illness. It is caused by many different germs. Hospital-acquired pneumonia tends to be more serious than other lung infections because:

·                     Patients in the hospital are often very sick and cannot fight off germs.

·                     The types of germs present in a hospital are often more dangerous than those encountered in the community.

Hospital-acquired pneumonia occurs more often in patients who are using a respirator machine to help them breathe. This machine is also called a ventilator. This type of pneumonia is known as ventilator-associated pneumonia.

Hospital-acquired pneumonia can also be spread by health care workers, who can pass germs from their hands or clothes from one patient to another. That is why hand-washing, wearing gowns, and using other safety measures is so important in the hospital.

Patients who are more prone to getting hospital-acquired pneumonia:

·                     Are alcoholic

·                     Have had chest surgery or other major surgery

·                     Have a weak immune system from cancer treatment, certain medicines, or severe wounds

·                     Have long-term (chronic) lung disease

·                     Breathe saliva or food into their lungs as a result of not being fully alert or problems swallowing

·                     Are older

 

Clinical picture.

People with infectious pneumonia often have a productive cough, fever accompanied by shaking chills, shortness of breath, sharp or stabbing chest pain during deep breaths, and an increased respiratory rate. In the elderly, confusion may be the most prominent sign. The typical signs and symptoms in children under five are fever, cough, and fast or difficult breathing.

Fever is not very specific, as it occurs in many other common illnesses, and may be absent in those with severe disease or malnutrition. In addition, a cough is frequently absent in children less than 2 months old. More severe signs and symptoms may include: blue-tinged skin, decreased thirst, convulsions, persistent vomiting, extremes of temperature, or a decreased level of consciousness

Bacterial and viral cases of pneumonia usually present with similar symptoms Some causes are associated with classic, but non-specific, clinical characteristics. Pneumonia caused by Legionella may occur with abdominal pain, diarrhoea, or confusion, while pneumonia caused by Streptococcus pneumoniae is associated with rusty colored sputum, and pneumonia caused by Klebsiella may have bloody sputum often described as “currant jelly”. Bloody sputum (known as hemoptysis) may also occur with Gram-negative pneumonia, and lung abscesses. Mycoplasma pneumonia may occur in association with swelling of the lymph nodes in the neck, joint pain, or a middle ear infection. Viral pneumonia presents more commonly with wheezing than does bacterial pneumonia.

Physical examination may sometimes reveal low blood pressure, high heart rate or low oxygen saturation. The respiratory rate may be faster than normal and this may occur a day or two before other signs. Examination of the chest may be normal, but may show decreased chest expansion on the affected side. Harsh breath sounds from the larger airways that are transmitted through the inflamed lung are termed bronchial breathing, and are heard on auscultation with a stethoscope. Crackles (rales) may be heard over the affected area during inspiration. Percussion may be dulled over the affected lung, and increased, rather than decreased, vocal resonance distinguishes pneumonia from a pleural effusion.

 

Lobar pneumonia

Stages.  The onset of the disease. Typical pneumonia begins abruptly with shaking chills, severe headache, and  fever (to 39-40 °C). The chills usually persist for 1-3 hours, then pain appears in the affected side; sometimes it may arise below the costal arch,   simulate acute appendicitis, hepatic colicks, etc. (this usually occurs in inflammation of the lower lobe of the lung, when the diaphagmatic pleura becomes involved in the process). Cough is first dry and in 1-2 days  rusty sputum is expectorated. The patient’s general condition is grave.

General examination shows hyperaemia of the cheeks, more pronounced on the affected side, dyspnoea, cyanosis, often herpes on the lips, nose; the affected side of the chest lags behind in the respiratory act.  Vocal fremitus is slightly exaggerated over the affected lobe. Sounds over lungs are quite varied and depend on the distribution of the process and stage of the disease, and other factors. At the onset of the disease, silent percussion sound can be heard over the affected lobe, often with panic effect because liquid and air are simultaneously contained in alveoli; the vesicular breathing is decreased while bronchophony is intensified; the so-called initial crepitation (crepitus indux) is present.

Lobes of the lungs

 

The height of the disease (classified by pathologists as the red and grey hepatization stages) is characterized by the grave general condition, will be explained not only by the size of the affected area of the lung which  does not take part in respiration but also by general toxicosis. Respiration is accelerated and superficial (30—40 per min) and tachycardia is characteristic. Dullness is heard over the affected lobe of the lung; bronchial respiration is revealed by auscultation; vocal fremutus and bronchophony are exaggerated. Vocal fremitus is in some cases till absent or enfeebled (in combination with pleurisy with effusion, and in massive acute lobar pneumonia, in which the inflammatory exudate in large bronchi); bronchial breathing is inaudible.

Stage of resolution shows normalixation of all pathological changes and final crepitation (crepitus redux).

 

Focal pneumonia

Pneumonia is typically diagnosed based on a combination of physical signs and a chest X-ray. However, the underlying cause can be difficult to confirm, as there is no definitive test able to distinguish between bacterial and non-bacterial origin. In adults, investigations are generally not needed in mild cases: there is a very low risk of pneumonia if all vital signs and auscultation are normal. In persons requiring hospitalization, pulse oximetry, chest radiography and blood tests—including a complete blood count, serum electrolytes, C-reactive protein level and possibly liver function tests—are recommended. The diagnosis of influenza-like illness can be made based on the signs and symptoms; however, confirmation of an influenza infection requires testing. Thus, treatment is frequently based on the presence of influenza in the community or a rapid influenza test.

 

Laboratory tests. In patients managed in the community, determining the causative agent is not cost effective and typically does not alter management. For people who do not respond to treatment, sputum culture should be considered, and culture for Mycobacterium tuberculosis should be carried out in persons with a chronic productive cough. Testing for other specific organisms may be recommended during outbreaks, for public health reasons. In those who are hospitalized for severe disease, both sputum and blood cultures are recommended, as well as testing the urine for antigens to Legionella and Streptococcus. Viral infections can be confirmed via detection of either the virus or its antigens with culture or polymerase chain reaction (PCR), among other techniques. The causative agent is determined in only 15% of cases with routine microbiological tests.

 

 

Microscopic examination of sputum shows neutrophils, macrophages and bacteria

 

A chest radiograph is frequently used in diagnosis. In people with mild disease, imaging is needed only in those with potential complications, those who have not improved with treatment, or those in which the cause in uncertain If a person is sufficiently sick to require hospitalization, a chest radiograph is recommended. Findings do not always correlate with the severity of a disease and do not reliably distinguish between bacterial infection and viral infection.

X-ray presentations of pneumonia may be classified as lobar pneumonia, bronchopneumonia (also known as lobular pneumonia), and interstitial pneumonia. Bacterial, community-acquired pneumonia, classically show lung consolidation of one lung segmental lobe which is known as lobar pneumonia. However, findings may vary, and other patterns are common in other types of pneumonia. Aspiration pneumonia may present with bilateral opacities primarily in the bases of the lungs and on the right side.Radiographs of viral pneumonia may appear normal, hyper-inflated, have bilateral patchy areas, or present similar to bacterial pneumonia with lobar consolidation. Radiologic findings may not be present in the early stages of the disease, especially in the presence of dehydration; or may be difficult to be interpreted in those who are obese or have a history of lung disease. A CT scan can give additional information in indeterminate cases.

Pneumonia of the right lower lobe

 

Pulmonary infiltration of the right lower lung lobe

 

Pneumonia of the right median lobe

 

 

 

 

Left sided pneumonia

 

 

 

 

Pleuropneumonia of the right upper lobe (the lower border is distinct due to affection of intercostal pleura)

 

 

Pleurisy with effusion as a result of pneumonia

 

 

Focal pneumonia

 

 

CT scan picture in pneumonia

 

Hospital pneumonia

Symptoms

In an elderly person, the first sign of hospital-acquired pneumonia may be mental changes or confusion. Other symptoms are:

·                     A cough that may produce mucus-like, greenish, or pus-like phlegm (sputum)

·                     Fever and chills

·                     General discomfort, uneasiness, or ill feeling (malaise)

·                     Loss of appetite

·                     Nausea and vomiting

·                     Sharp chest pain that gets worse with deep breathing or coughing

·                     Shortness of breath

Exams and Tests

Tests to check for hospital-acquired pneumonia may include:

·                     Arterial blood gases, to measure oxygen levels in the blood

·                     Blood cultures, to see if the infection has spread to the blood

·                     Chest x-ray or CT scan, to check the lungs 

·                     Complete blood count (CBC)

·                     Pulse oximetry, to measure oxygen levels in the blood

·                     Sputum culture or sputum gram stain, to check for what germs are causing the pneumonia

 

ASPIRATION PNEUMONIA

Aspiration pneumonia is an especially severe type of pneumonia, often with a high mortality rate. It results from the aspiration of gastric contents in addition to aspiration of upper respiratory flora in secretions. Important predisposing factors include impairment of the swallowing mechanism (eg, esopha- geal disease), inadequate cough reflex (eg, anesthesia, postoperative state, central nervous system disease, drug abuse), and impaired gastric emptying (eg, pyloric obstruction). Pulmonary injury is due in large part to the low pH (< 2.5) of gastric secretions.

Scattered areas of pulmonary edema and bron- chospasm occur, and the x-ray appearance may be confused with that of pulmonary emboli, atelectasis, bronchopneumonia, and congestive heart failure.

 

Abscess is forming after aspiration

 

 

 Right sided aspiration pneumonia

 

Infection in the immunocompromized host

Pneumonia in people whose immune system is weakened (for example, by AIDS, organ transplantation, or the use of certain drugs) is usually caused by different organisms than those that cause pneumonia in healthy people.

·                Pneumocystis jiroveci pneumonia often occurs in people who have a weakened immune system.

·                People have shortness of breath, a dry cough, and often fever.

·                X-rays of the chest are not as helpful as microscopic examinations of sputum samples for making the diagnosis.

·                Trimethoprim-sulfamethoxazole is often used to treat this pneumonia.

Pneumocystis jiroveci is a common fungus that may reside harmlessly in the lungs of healthy people. It usually causes pneumonia only when the body’s defenses are weakened because of cancer, drugs that alter the immune system, or AIDS. Drugs that alter the immune system include corticosteroids, chemotherapy drugs, and drugs used to treat autoimmune disorders. Often, P. jiroveci pneumonia is the first indication that a person with human immunodeficiency virus (HIV) infection has developed AIDS.

Most people develop a fever, shortness of breath, and a dry cough. These symptoms usually arise over several weeks. The lungs may not be able to deliver sufficient oxygen to the blood, leading to shortness of breath that is sometimes severe.

X-rays show either no abnormality or patchy infection, similar to that which occurs in some viral infections. The diagnosis is made by microscopic examination of expectorated sputum or from sputum obtained by induction (in which a vapor is used to stimulate coughing) or bronchoscopy (in which an instrument is inserted into the airways to collect a specimen—see Diagnosis of Lung Disorders: Bronchoscopy).

Clinical pattern of pneumonia depending on its etiology

PNEUMOCOCCAL PNEUMONIA

Essentials of Diagnosis

• Sudden onset of shaking chills, fever, chest pain, and cough with rust-colored sputum.

• X-rays show infiltration, often lobar in distribu- tion, but sometimes patchy.

• Pneumococci are present in the sputum and often in the blood.

• Leukocytosis.

General Considerations

Pneumonia is an inflammatory process in lung parenchyma most commonly caused by infection. The consolidation of pneumonia must be differentiated from pulmonary infarction, atelectasis with bronchial obstruction, and congestive heart failure, but it may coexist with any of these conditions. The pneumococcus accounts for 50-80% of community-acquired bacterial pneumonias; types 1-9 and 12 are most commonly found in adults, whereas types 6, 14, 19, and 23 are most common in children. These bacteria frequently are in the normal flora of the respiratory tract. The development of pneumonia must therefore usually be attributed to an impairment of natural resis- tance. Conditions leading to aspiration of secretions include suppression of the cough or epiglottic reflex, impairment of upward migration of mucous sheets (propelled by cilia), and impairment of alveolar phagocyte function. Among conditions that predis- pose to pneumonia are viral respiratory diseases, mal- nutrition, exposure to cold, noxious gases, alcohol intoxication, depression of cerebral functions by drugs, and cardiac failure. Pulmonary consolidation may be in one or more lobes or may be patchy in distribution.

Clinical Findings

Symptoms and Signs: The onset is usually sudden, with shaking chills, “stabbing” chest pain (exaggerated by respiration but sometimes referred to the shoulder, abdomen, or flank), high fever, cough and “rusty” sputum, and occasionally vomiting. A history of recent upper respiratory illness can often be elicited.

The patient appears severely ill, with marked tachypnea (30-40/min) but no orthopnea. Respi- rations are grunting, nares flaring, and the patient often lies on the affected side in an attempt to splint the chest. Herpes simplex facial lesions are often present.

Initially, chest excursion is diminished on the involved side, breath sounds are suppressed, and fine inspiratory rales are heard. Later, the classic signs (absent breath sounds, dullness, etc) of consolidation appear. A pleural friction rub or abdominal distention may be present. During resolution of the pneumonia, the signs of consolidation are replaced by rales. Physical findings are often inconclusive, and repeated x-ray examination is helpful.

Laboratory Findings: Blood cultures are positive for pneumococci in 15-25% of cases early in the disease. In peripheral blood, leukocytosis (20-35 thousand/^L) is the rule, and a low white blood cell count carries a poorer prognosis.

Sputum must be examined by Gram’s stain and by culture. In the smears, the presence of many squamous epithelial cells suggests heavy contamination with saliva, and such specimens are of no value. Typical sputum from pneumococcal pneumonia contains many red and white cells (PMNs) and many pneumococci. If good sputum specimens are not obtainable, a trans- tracheal aspirate may reveal the causative agent, but this procedure is not without risk. A microscopic “quellung” reaction with pooled antiserum rapidly identifies pneumococci in fresh sputum.

X-Ray Findings Initially, there may be only a vague haziness across the involved part of the lung field. Later typical consolidation is well defined either in lobar or in patchy distribution. Fluid shadows in the costophrenic angles may appear before pleural exudate can be detected by physical examination. During reso lution of the consolidation, which may require 8-10 weeks, areas of radiolucency may appear, suggesting ‘ ‘pseudocavitation.”

 

OTHER BACTERIAL PNEUMONIAS

Primary bacterial pneumonias caused by single bacterial species other than the pneumococcus may account for up to 25% of community-acquired and 80% of hospital-acquired pneumonias. All of these pneumonias may have somewhat similar physical find- ings and x-ray evidence of pulmonary infiltration or •consolidation. For proper treatment, it is crucial to identify the causative agent by blood culture and by sputum examination with stained smear and culture. Transtracheal aspiration, fiberoptic bronchoscopy, or even lung biopsy may be needed for specific diagnosis and treatment.

Streptococcal Pneumonia

Pneumonia due to hemolytic streptococci occurs usually as a sequela to viral infection of the respiratory tract, especially influenza or measles, or in persons with underlying pulmonary disease. The patients are usually in a severely toxic condition and cyanotic. Pleural effusion develops frequently and early and progresses to empyema in one-third of untreated pa- tients. The diagnosis rests on finding large numbers of streptococci in smears of sputum and culturing hemolytic streptococci from blood and sputum.

The treatment of choice is with penicillin G in a dosage similar to that for pneumococcal pneumonia (see above). If treatment is started early, the prognosis is good.

Staphylococcal Pneumonia

Pneumonia caused by Staphylococcus aureus occurs as a sequela to viral infections of the respiratory tract (eg, influenza) and in debilitated (eg, postsurgical) patients or hospitalized infants, especially after antimicrobial drug administration. There is often a history of a mild illness with headache, cough, and generalized aches that abruptly changes to a very se- vere illness with high fever, chills, and exaggerated cough with purulent or blood-streaked sputum and deep cyanosis. There may be early signs of pleural effusion, empyema, or tension pneumothorax. X-ray examination reveals lung consolidation, pneumatoceles, abscesses, empyema, and pneumothorax. The demonstration of pyopneumothorax and of cavities with air-fluid levels by x-ray is highly suggestive of Staphylococcal pneumonia. The diagnosis must be confirmed by stained smear of sputum (masses of white cells and gram-positive cocci, many intra- cellular) and culture (predominantly S aureus), and also by means of cultures of pleural fluid and blood. The white count is usually more than 20,000//zL.

 

The patchy infiltrates bilaterally with the right greater than the left containing air bronchograms are characteristic of a bilateral pneumonic process which extends into the alveolar spaces.

 

Legionella Pneumonia

The eponym legionnaires’ disease has been given to a serious pneumonia that afflicted people attending the American Legion Convention in Philadelphia in 1976. Other outbreaks have been diagnosed ret- rospectively at least since 1965, and sporadic infec- tions have occurred at least since 1947 in many places.

Legionella pneumophila is a poorly staining gram-negative bacterium that grows slowly on special media (eg, charcoal-yeast extract) at 35 °C. There are at least 8 species of Legionella, some with multiple serotypes. These organisms can be recovered in human disease from sputum, bronchial washings, pleural fluid, lung biopsies, or blood. Legionella species occur in the environment and are acquired by humans from aerosols, dust from air-conditioning systems, water, or soil. The infection is not usually communi- cable from patient to contacts. Asymptomatic infec- tion is common at all ages, whereas symptomatic infection is most often an opportunistic pneumonia in immunocompromised individuals.

Asymptomatic infection is evident only by a rise in specific antibodies. Symptomatic infection is ob- served mainly in elderly persons, smokers, and pa- tients undergoing hemodialysis or renal transplant.

The incubation period is estimated to be 2-10 days. Initial symptoms are malaise, diffuse myalgias, and headache, followed in 12-48 hours by high, non- remittent fever and chills. Nausea, vomiting, and diarrhea are frequent early in the illness. On the third day a dry cough begins that is nonproductive or produces scanty mucoid, sometimes blood-streaked sputum. Dyspnea and hypoxia become marked as signs of consolidation develop. Pleuritic chest pain occurs in one-third of patients. Severe confusion or delirium may occur.

There is leukocytosis with a shift to the left, hyponatremia, abnormal liver function tests, and, occasionally, microscopic hematuria. Chest x-rays reveal patchy, often multilobar pulmonary consolidation, and, occasionally, small pleural effusions. The illness usually worsens for 4-7 days before improvement begins in those who recover. During severe outbreaks, the mortality rate has been 10% in those with manifest disease. Death is attributed to respiratory or renal failure or shock, with disseminated intravascular coagulation.

The diagnosis is based on a clinical picture compatible with the specific features of the disease and oegative results of bacteriologic laboratory tests for other pneumonias. The organism can be identified by immunofluorescence in cultures, lung biopsy, and, rarely, sputum specimens. A retrospective diagnosis is based on a significant rise in specific serum antibodies detected by immunofluorescence.

 

Pneumocystis carinii Pneumonia

This parasitic infection occurs in debilitated children or immunodeficient adults. It has been a prominent opportunistic infection in AIDS patients. The diagnosis is made by lung biopsy and the demonstration of typical cysts of P carinii in impression smears of lung tissue stained with methena- mine-silver.

 

“MIXED” BACTERIAL PNEUMONIAS (Hypostatic Pneumonia, “Terminal” Pneumonia, Bronchopneumonia)

Essentials of Diagnosis

• Variable onset of fever, cough, dyspnea, expectoration.

• Symptoms and signs often masked by primary (debilitating) disease.

• Greenish-yellow sputum (purulent) with mixed flora.

• Leukocytosis (often absent in aged and debilitated patients).

• Patchy infiltration on chest x-ray.

General Considerations

Mixed bacterial pneumonias include those in which culture and smear reveal several organisms, not one of which can clearly be identified as the causative agent. These pneumonias usually appear as complica- tions of anesthesia, surgery, aspiration, trauma, or various chronic illnesses (cardiac failure, advanced carcinoma, uremia). They are common complications of chronic pulmonary diseases such as bronchiectasis and emphysema. Old people are most commonly affected (“terminal” pneumonia). Patients treated with intermittent positive pressure breathing apparatus or immunosuppressive drugs may develop pneumonia caused by gram-negative rods.

The following findings in a debilitated, chroni- cally ill, or aged person suggest a complicating pneumonia: (1) worsening of cough, dyspnea, cyanosis; (2) low-grade, irregular fever; (3) purulent sputum; and (4) patchy basal densities on a chest film (in addition to previously noted densities caused by a primary underlying disease, if any), sometimes with local necrosis and cavitation.

Clinical Findings

Symptoms and Signs: The onset is usually insidious, with low-grade fever, cough, expectoration, and dyspnea that may become marked and lead to cyanosis. Physical findings are extremely variable and may not be impressive against a background of cardiac or pulmonary disease. The signs listed under Other Bacterial Pneumonias may also be present.

Laboratory Findings: The appearance of a greenish or yellowish (purulent) sputum should suggest a complicating pneumonia. Smears and cul- tures reveal a mixed flora, often including anaerobes. Predominant types should be noted. Leukocytosis is often absent in the aged and debilitated patient presenting with a mixed infection.

X-Ray Findings: X-ray shows patchy, irregular infiltrations, most commonly posterior and basal (in bedridden patients). Abscess formation may be observed. Careful interpretation will avoid confusion with shadows due to preexisting heart or lung disease.

 

Hypostatic pneumonia

 

Differential Diagnosis

Mixed bacterial pneumonias must be differ- entiated from tuberculosis, carcinoma, and other spe- cific mycotic, bacterial, and viral pulmonary infections (to which they may be secondary).

Viral Pneumonias

Viruses are a common cause of serious infections of the lower respiratory tract among immunocompromised patients. Pathogens most commonly implicated are the herpesviruses–herpes simplex, varicella-zoster, and cytomegalovirus. These viruses belong to the family Herpesviridae, which consists of large, enveloped, double-stranded DNA viruses.

Herpesviruses vary widely in their ability to infect different types of cells. Further, they share the common ability to establish lifelong latent infection. This latter aspect is of particular concern for seropositive immunosuppressed persons, whose immune systems may be unable to contain the virus in its latent form.

Other viruses that cause significant lower respiratory tract disease in immunocompromised patients include adenoviruses and measles virus.

Epidemiologic, etiologic, and clinical characteristics       
Immunocompromised patients are at particular risk for virus pneumonia. These include patients who are receiving cancer chemotherapy, those who are neutropenic, those infected with HIV, burn victims, those with congenital cell-mediated immunodeficiency, and those who are severely debilitated or malnourished as a result of prolonged hospitalization. Although the lung is often involved in disseminated HSV infection, disseminated disease seldom occurs among those with mucocutaneous HSV infections. Visceral dissemination develops in fewer than 10% of virus -seropositive transplant recipients with infection.

HSV pneumonia develops by two principal mechanisms. First, the presence of focal or multifocal infiltrates correlates with antecedent upper airway infection with virus. This pattern is most likely due to direct extension of viral infection from the upper to the lower respiratory tract, aspiration of infectious secretions, or reactivation of dormant HSV in vagal ganglia. Tracheitis or esophagitis and oral mucocutaneous lesions often precede development of pulmonary disease. Second, diffuse interstitial infiltrates may develop following viremia secondary to dissemination of HSV from genital or oral lesions or transfusion of HSV-infected blood. Early dissemination also may be reflected by other organ dysfunction, such as elevated liver enzyme levels.

The spectrum of respiratory diseases due to HSV infection ranges from oropharyngitis to membranous tracheobronchitis and diffuse or localized pneumonia. Usually the trachea and large bronchi are involved in creating a thick inflammatory membrane that can ultimately cause significant resistance to ventilation. Community-acquired pneumonia caused by HSV is uncommon, occurring usually only after a prolonged and complicated hospital stay.

Dyspnea and cough are the most common symptoms of HSV pneumonia. Fever, tachypnea, intractable wheezing, chest pain, and hemoptysis also occur. Cutaneous, genital, or oral lesions may herald pulmonary or disseminated disease.

Focal lesions on chest film begin as small nodules that are best seen in the periphery, away from normal vascular markings. As the disease progresses, the nodules may coalesce to form extensive infiltrates. HSV pneumonia may initially present as a focal or segmental pneumonia that has spread from upper airway lesions. However, it can ultimately extend to other areas of the lung, producing diffuse infiltrates similar to the pattern seen with viremic HSV infection.

Diagnosis
The diagnosis of virus pneumonia should be based on clinical suspicion, radiographic findings (picture 6), isolation of HSV from the lungs, and histologic findings of a necrotizing or hemorrhagic pneumonia. Since virus can be isolated from oropharyngeal secretions in 2% to 25% of normal hosts, positive sputum cultures are often difficult to interpret. The use of tracheal aspirates to bypass the upper respiratory tract can yield samples with significantly improved specificity. Bronchoscopy is especially useful for direct sampling of bronchial mucosal lesions and for obtaining bronchial brushings, washings, and biopsy specimens for histologic and cytologic examination. Scrapings from the base of ulcerated lesions can be examined with Wright or Giemsa stain for multinucleated giant cells and intranuclear inclusions. Specimens also can be examined by immunofluorescent staining with polyclonal- or monoclonal-specific antibodies or by electron microscopy. Appropriate viral cultures of mucosal lesions, blood, and respiratory secretions should always be obtained in cases of suspected herpetic pneumonia. Serologic assays are of little diagnostic use.

A-normal chest X –ray; B-right sided viral pneumonia

 

Differential diagnosis. Several diseases can present with similar signs and symptoms to pneumonia, such as: chronic obstructive pulmonary disease (COPD), asthma, pulmonary edema, bronchiectasis, lung cancer, and pulmonary emboli. Unlike pneumonia, asthma and COPD typically present with wheezing, pulmonary edema presents with an abnormal electrocardiogram, cancer and bronchiectasis present with a cough of longer duration, and pulmonary emboli presents with acute onset sharp chest pain and shortness of breath.

Complications. Pleural effusion, empyema, and abscess

A pleural effusion: as seen on chest x-ray. The A arrow indicates fluid layering in the right chest. The B arrow indicates the width of the right lung. The volume of the lung is reduced because of the collection of fluid around the lung.

In pneumonia, a collection of fluid may form in the space that surrounds the lung. Occasionally, microorganisms will infect this fluid, causing an empyema. To distinguish an empyema from the more common simple parapneumonic effusion, the fluid may be collected with a needle (thoracentesis), and examined. If this shows evidence of empyema, complete drainage of the fluid is necessary, often requiring a drainage cathater. In severe cases of empyema, surgery may be needed. If the infected fluid is not drained, the infection may persist, because antibiotics do not penetrate well into the pleural cavity. If the fluid is sterile, it needs to be drained only if it is causing symptoms or remains unresolved.

Rarely, bacteria in the lung will form a pocket of infected fluid called a lung abscess. Lung abscesses can usually be seen with a chest X-ray but frequently require a chest CT scan to confirm the diagnosis. Abscesses typically occur in aspiration pneumonia, and often contain several types of bacteria. Long term antibiotics are usually adequate to treat a lung abscess, but sometimes the abscess must be drained by a surgeon or radiologist.

 

Respiratory and circulatory failure

Pneumonia can cause respiratory failure by triggering acute respiratory distress syndrome (ARDS), which results from a combination of infection and inflammatory response. The lungs quickly fill with fluid and become stiff. This stiffness, combined with severe difficulties extracting oxygen due to the alveolar fluid, may require long periods of mechanical ventilation for survival.

Sepsis is a potential complication of pneumonia but occurs typically only in people with poor immunity or hyposplenism. The organisms most commonly involved are Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae. Other causes of the symptoms should be considered such as a myocardial infarction or a pulmonary embolism.

 

Treatment of pneumonia

Bacterial

Antibiotics improve outcomes in those with bacterial pneumonia. Antibiotic choice depends initially on the characteristics of the person affected, such as age, underlying health, and the location the infection was acquired. In the UK, empiric treatment with amoxicillin is recommended as the first line for community-acquired pneumonia, with doxycycline or clarithromycin as alternatives. In North America, where the “atypical” forms of community-acquired pneumonia are more common, macrolides (such as azithromycin or erythromycin), and doxycycline have displaced amoxicillin as first-line outpatient treatment in adults. In children with mild or moderate symptoms amoxicillin remains the first line. The use of fluoroquinolones in uncomplicated cases is discouraged due to concerns about side effects and generating resistance in light of there being no greater clinical benefit. The duration of treatment has traditionally been seven to ten days, but increasing evidence suggests that shorter courses (three to five days) are similarly effective. Recommended for hospital-acquired pneumonia include third- and fourth-generation cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and vancomycin. These antibiotics are often given intravenously and used in combination. In those treated in hospital more than 90% improve with the initial antibiotics.

Viral

Neuraminidase inhibitors may be used to treat viral pneumonia caused by influenza viruses (influenza A and influenza B). No specific antiviral medications are recommended for other types of community acquired viral pneumonias including SARS coronavirus, adenovirus, hantavirus, and parainfluenza virus. Influenza A may be treated with rimantadine or amantadine, while influenza A or B may be treated with oseltamivir, zanamivir or peramivir. These are of most benefit if they are started within 48 hours of the onset of symptoms. Many strains of H5N1 influenza A, also known as avian influenza or “bird flu,” have shown resistance to rimantadine and amantadine.[6] The use of antibiotics in viral pneumonia is recommended by some experts as it is impossible to rule out a complicating bacterial infection. The British Thoracic Society recommends that antibiotics be withheld in those with mild disease.[6] The use of corticosteroids is controversial.

Aspiration

In general, aspiration pneumonitis is treated conservatively with antibiotics indicated only for aspiration pneumonia. The choice of antibiotic will depend on several factors, including the suspected causative organism and whether pneumonia was acquired in the community or developed in a hospital setting. Common options include clindamycin, a combination of a beta-lactam antibiotic and metronidazole, or an aminoglycoside. Corticosteroids are sometimes used in aspiration pneumonia, but there is limited evidence to support their effectiveness.

Prevention includes vaccination, environmental measures and appropriate treatment of other health problems. It is believed that if appropriate preventive measures were instituted globally, mortality among children could be reduced by 400,000 and if proper treatment were universally available, childhood deaths could be decreased by another 600,000.

Vaccination

Vaccination prevents against certain bacterial and viral pneumonias both in children and adults. Influenza vaccines are modestly effective against influenza A and B. The Center for Disease Control and Prevention (CDC) recommends yearly vaccination for every person 6 months and older. Immunizing health care workers decreases the risk of viral pneumonia among their patients. When influenza outbreaks occur, medications such as amantadine or rimantadine may help prevent the condition. It is unknown if zanamivir or oseltamivir are effective due to the fact that the company that manufactures oseltamivir has refused to release the trial data for independent analysis.

Vaccinations against Haemophilus influenzae and Streptococcus pneumoniae have good evidence to support their use. Vaccinating children against Streptococcus pneumoniae has led to a decreased incidence of these infections in adults, because many adults acquire infections from children. A Streptococcus pneumoniae vaccine is available for adults, and has been found to decrease the risk of invasive pneumococcal disease. Other vaccines for which there to support for a protective effect against pneumonia include: pertussis, varicella, and measles.

Other

Smoking cessation and reducing indoor air pollution, such as that from cooking indoors with wood or dung, are both recommended. Smoking appears to be the single biggest risk factor for pneumococcal pneumonia in otherwise healthy adults. Hand hygiene and coughing into ones sleeve may also be effective preventative measures. Wearing surgical masks by those who are sick may also prevent illness.

Appropriately treating underlying illnesses (such as HIV/AIDS, diabetes mellitus, and malnutrition) can decrease the risk of pneumonia. In children less than 6 months of age exclusive breast feeding reduces both the risk and severity of disease. In those with HIV/AIDS and a CD4 count of less than 200 cells/uL the antibiotic trimethoprim/sulfamethoxazole decreases the risk of  and may also be useful for prevention in those who are immunocomprised but do not have HIV.

Testing pregnant women for Group B Streptococcus and Chlamydia trachomatis, and administering antibiotic treatment, if needed, reduces rates of pneumonia in infants; preventive measures for HIV transmission from mother to child may also be efficient. Suctioning the mouth and throat of infants with meconium-stained amniotic fluid has not been found to reduce the rate of aspiration pneumonia and may cause potential harm, thus this practice is not recommended in the majority of situations. In the frail elderly good oral health care may lower the risk of aspiration pneumonia.

Hospital pneumonia.

Treatment

You will receive antibiotics through your veins (IV) to treat your lung infection. The antibiotic you are given will fight the germs that are in your sputum culture.

You may also receive oxygen to help you breathe better and lung treatments to loosen and remove thick mucus from your lungs.

Patients who have other serious conditions do not recover as well from pneumonia as patients who are not as sick.

Outlook (Prognosis)

Hospital-acquired pneumonia can be a life-threatening illness. Long-term lung damage may occur.

Prevention

Wash your hands for at least 1 minute, like this:

·  Lather up well with warm water and soap.

·  Wash the backs and palms of your hands, fingers, between your fingers, and under your nails thoroughly.

·  Wash for as long as it takes you to say the alphabet slowly or sing the “Happy Birthday” song 2 times through.

·  Dry with a clean paper towel. Also, use a paper towel to turn off the faucet and open the bathroom door.

After any surgery, you will be asked to take deep breaths to help keep your lungs open. Follow the advice of your doctor and nurse to help prevent pneumonia.

Most hospitals have programs to prevent hospital-acquired infections.

 

Aspiration pneumonia/

Treatment

Removal of aspirated material by catheter suction or bronchoscopy may be attempted, but this usually fails to remove all aspirate completely. Corticosteroids (eg, prednisone, 100 mg orally on the first or second day) may reduce the intensity of the inflammatory reaction to acidic gastric secretion, but the value of corticosteroids in the treatment of aspiration pneumo- nia is not proved, and they increase the risk of superinfection. Some aspiration pneumonias have no bacterial component, but in many others a mixed bacterial flora is involved. Antimicrobial drugs directed against the latter (eg, penicillin G plus an aminoglycoside or the best available cephalosporin) are sometimes adminis- tered without waiting for evidence of progressive pul- monary infection. In doing so, however, there is a risk of favoring the development of resistant microorganisms. Therefore, administration of antimi-crobials should not continue without laboratory and clinical evidence of microbial infection. Assisted ventilation and supplementary oxygen are beneficial.

Infection in the immunocompromised host

Treatment

The combination antibiotic trimethoprim-sulfamethoxazole can be used to help prevent Pneumocystis pneumonia in people at risk. This drug’s side effects, which are particularly common in people who have AIDS, include rashes, a reduced number of infection-fighting white blood cells, and fever. Alternative preventive drug treatments are dapsone , atovaquone , and pentamidine (which can be taken as an aerosol, inhaled directly into the lungs).

Drugs used to treat Pneumocystis pneumonia are trimethoprim-sulfamethoxazole , dapsone combined with trimethoprim, clindamycin and primaquine, atovaquone , or intravenous pentamidine . When the level of oxygen in the blood falls below a certain level, corticosteroids may also be given.

Even when the pneumonia is treated, the overall death rate is 15 to 20%.

Staphylococcal Pneumonia

Initial therapy (based on sputum smear) consists of nafcillin, 6-12 g/d, or vancomycin, 2 g/d, given intravenously in divided doses as a bolus. If the staphylococcus proves to be penicillin-sensitive by laboratory test, penicillin G, 20-60 million units/d intravenously, is the antibiotic of choice. Drugs should be continued for several weeks. If empyema develops, drainage must be established. The prognosis varies with the underlying condition of the patient and the drug susceptibility of the organism.

 

Legionella Pneumonia

The treatment of choice is erythromycin, 0.5-1 g every 6 hours intravenously or orally for 2-3 weeks. This usually results in improvement in 2-3 days. Rifampin, 10-20 mg/kg/d, has been suggested for patients who fail to respond to erythromycin. Assisted ventilation and management of shock are essential.

 

Pneumocystis carinii Pneumonia

Early treatment with sulfamethoxazole- trimethoprim can cure the pneumonia. The same drug has been effective in prophylaxis during immunosuppression. An alternative, more toxic drug is pentamidine isethionate (available through the Centers for Disease Control, Atlanta, GA 30333).

 

“MIXED” BACTERIAL PNEUMONIAS

Clear the airway and correct hypoxia. Unless a probably significant etiologic agent can be identified, give one of the new cephalosporins (eg, cefotaxime, 12 g/d intravenously) as initial therapy. This will be modified according to clinical and laboratory results.

Viral Pneumonias

Treatment

Antibiotics. The Infectious Diseases Society of America recommends selecting from among the macrolides erythromycin, clarithromycin (Biaxin), and azithromycin (Zithromax); the fluoroquinolones levofloxacin (Levaquin), trovafloxacin mesylate (Trovan), grepafloxacin (Raxar), sparfloxacin (Zagam), and any other fluoroquinolone with enhanced activity against S pneumoniae; and (in patients between the ages of 17 and 40) doxycycline.

Duration of therapy  The preferred duration of therapy for community-acquired pneumonia is an unresolved issue, and surprisingly, applicable prospective studies are not available. The Infectious Diseases Society of America recommends 7 to 10 days. However, one study found that clinical outcomes were as good with a 3- to 5-day course of azithromycin as with the usual 7- to 10-day course of comparable antibiotics. Outcome research is urgently needed, because both cost and resistance could be minimized by using shorter courses of antibiotic therapy.

Antibiotic resistance

Development of bacterial resistance has been a significant problem related to antibiotic use. The frequency of resistance among community-acquired pathogens is increasing and has been linked to inappropriate use of antibiotics, such as the following:

To treat viral infections

To treat resistant organisms

For longer periods thaecessary

To treat a particular organism with a much-wider-spectrum agent than needed

Unnecessary use of antibiotics for viral illnesses is common and has led to increasing rates of antibiotic resistance among S pneumoniae and other community-acquired pathogens. In addition, boundaries between community and hospital environments are blurring, with potential negative consequences regarding resistance. Resistance genes occur in both pathogenic and commensal organisms to which people are exposed continually through food, the environment, and animals. The multitude of genetic mechanisms available for evolution and reassortment of antibiotic resistance genes virtually ensures that genes useful to survival of bacteria are rapidly disseminated.

Resistance to different antibiotics may vary by hospital and by locale, so the pattern of resistance in a geographic area of practice must be known to make a rational selection among antibiotics. Information on resistance patterns can be obtained from each hospital’s microbiology department and each state’s board of health.

Surveillance studies show almost exponential increases in penicillin-resistant S pneumoniae over the past 3 years in the United States. This trend is also true worldwide. If a location has considerable (eg, more than 5% to 10%) resistance to S pneumoniae, use of another antibiotic should be considered. High-level resistance to penicillin is associated with high-level resistance to macrolides, cephalosporins, and doxycycline as well. In contrast, to date, high-level resistance to the newer fluoroquinolones is less than 1%, and cross-resistance between these agents and penicillin has not, as yet, been recognized.

 

Prognosis

The prognosis depends upon the nature and sever- ity of the underlying pulmonary disease and varies with the predominating organism.

 

Minimizing resistance          Theoretically, choosing doses of antibiotics on the basis of pharmacodynamics should increase eradication of bacteria and thus minimize development of resistance. Preventing antibiotic resistance through rapid DNA-based testing is an emerging and potentially promising biotechnologic tool. Additional new techniques under way to combat resistance include development of products that block bacterial adherence to tissues, design of drugs to fit model chemicals into the crystal structures of the catalytic sites of key enzymes from bacteria, and use of other highly sophisticated molecular biology tools.

More general solutions to the problem of increasing antibiotic resistance include intensive education of healthcare providers, enhanced education of patients, institution of mandatory surveillance programs, and funding of appropriate research.

Typically, oral antibiotics, rest, simple analgesics, and fluids suffice for complete resolution. However, those with other medical conditions, the elderly, or those with significant trouble breathing may require more advanced care. If the symptoms worsen, the pneumonia does not improve with home treatment, or complications occur, hospitalization may be required. Worldwide, approximately 7–13% of cases in children result in hospitalization while in the developed world between 22 and 42% of adults with community-acquired pneumonia are admitted. The CURB-65 score is useful for determining the need for admission in adults. If the score is 0 or 1 people can typically be managed at home, if it is 2 a short hospital stay or close follow-up is needed, if it is 3–5 hospitalization is recommended. In children those with respiratory distress or oxygen saturations of less than 90% should be hospitalized. The utility of chest physiotherapy in pneumonia has not yet been determined. Non-invasive ventilation may be beneficial in those admitted to the intensive care unit There is insufficient evidence for mucolytics.

·                Complications of pneumonia

Complications may occur particularly in the elderly and those with underlying health problems. This may include, among others: empyema, lung abscess, bronchiolitis obliterans, acute respiratory distress syndrome, sepsis, and worsening of underlying health problems.

Clinical prediction rules have been developed to prognosticate more objectively outcomes in pneumonia. These rules are often used in deciding whether or not to hospitalize the person.

·                Pneumonia severity index (or PSI Score)

·                CURB-65 score, which takes into account the severity of symptoms, any underlying diseases, and age

 

 

Pleurisy

Pleurisy (also known as pleuritis) is an inflammation of the pleura, the lining of the pleural cavity surrounding the lungs. Among other things, infections are the most common cause of pleurisy.

The inflamed pleural layers rub against each other every time the lungs expand to breathe in air. This can cause severe sharp pain with inhalation (also called pleuritic chest pain).

The main symptom of pleurisy is a sharp, stabbing pain in the chest that gets worse with deep breathing, coughing, sneezing, or laughing. The pain may stay in one place, or it may spread to the shoulder or back. Sometimes, it becomes a fairly constant dull ache.

Depending on its cause, pleurisy may be accompanied by other symptoms:

•      Coughing, which may produce blood

•      Fever and chills

•      Rapid, shallow breathing

•      Shortness of breath

•      Sore throat followed by pain and swelling in the joints

•      Ventricular tachycardia

A diagnosis of pleurisy or another pleural condition is based on a medical history, a physical examinations, and diagnostic tests. The goals are to rule out other sources of the symptoms and to find the cause of the pleurisy so that the underlying disorder can be treated.

Physical examination

A doctor uses a stethoscope to listen to the breathing. This method detects any unusual sounds in the lungs. A person with pleurisy may have inflamed layers of the pleura that make a rough, scratchy sound as they rub against each other during breathing. This is called pleural friction rub.

 

        

 

Diagnostic tests

Depending on the results of the physical examination, diagnostic tests are sometimes performed.

Chest x-ray

A chest x-ray takes a picture of the heart and lungs. It may show air or fluid in the pleural space. It also may show the cause (e.g. pneumonia, a fractured rib, or a lung tumor) of the pleurisy.

Sometimes an x-ray is taken while lying on the painful side. This may show fluid, as well as changes in fluid position, that did not appear in the vertical x-ray.

Computed tomography (CT) scan

A CT scan provides a computer-generated picture of the lungs that can show pockets of fluid. It also may show signs of pneumonia, a lung abscess, or a tumor.

Ultrasound

Ultrasonography uses sound waves to create an image. It may show where fluid is located in the chest. It also can show some tumors. Although ultrasound may detect fluid around the lungs, also known as a pleural effusion, sound waves cannot penetrate bone. Therefore, an actual picture of the lungs cannot be obtained with ultrasonography.

Magnetic Resonance Imaging (MRI)

Magnetic resonance imaging (MRI), also called nuclear magnetic resonance (NMR) scanning, uses powerful magnets to show pleural effusions and tumors.

Blood Test

A blood tests can detect bacterial or viral infections, pneumonia, rheumatic fever, a pulmonary embolism, or lupus.

Arterial Blood Gas

In arterial blood-gas sampling, a small amount of blood is taken from an artery, usually in the wrist. The blood is then checked for oxygen and carbon-dioxide levels. This test shows how well the lungs are taking in oxygen.

Thoracentesis

 

The illustration shows a person undergoing thoracentesis. The person sits upright and leans on a table. Excess fluid from the pleural space is drained into a bag.

Once the presence and location of fluid is confirmed, a sample of fluid can be removed for testing. The procedure to remove fluid in the chest is called thoracentesis. The doctor inserts a small needle or a thin, hollow, plastic tube in the chest wall and withdraws fluid.

Thoracentesis can be done in the doctor’s office or at the hospital. Ultrasound is used to guide the needle to the fluid that is trapped in small pockets around the lungs.

Thoracentesis usually does not cause serious complications. Generally, a chest x-ray is done after the procedure to evaluate the lungs. Possible complications of thoracentesis include the following:

·                     Bleeding and bruising where the needle went in. In rare cases, bleeding may occur in or around the lung. The doctor can use a chest tube to drain the blood. In some cases, surgery is needed.

·                     Infection where the needle went in

·                     Injury to the liver or spleen (in rare cases)

·                     Pain

·                     Pneumothorax, or buildup of air in the pleural space, with a collapsed or partially collapsed lung. Sometimes air comes in through the needle or the needle makes a hole in the lung. Usually, a hole will seal itself. But sometimes air can build up around the lung and make it collapse. A chest tube can remove the air and let the lung expand again.

The lung fluid is examined under a microscope and is evaluated for the presence of chemicals and for its color and texture. The degree of clarity is an indicator of infection, cancer, or other conditions that may be causing the buildup of fluid or blood in the pleural space.

Biopsy

If tuberculosis or cancer is suspected, a small piece of the pleura may be examined under a microscope to make a definitive diagnosis. This is called a biopsy.

Several approaches to taking tissue samples are available

1.                 Insertion of a needle through the skin on the chest to remove a small sample of the outer layer of the pleura.

2.                 Insertion of a small tube with a light on the end (endoscope) into tiny cuts in the chest wall in order to visualize the pleura. Small pieces of tissue can be biopsied though the endoscope.

3.                 remove a sample of the pleura through a small cut in the chest wall. This is called an open pleural biopsy. It is usually done if the sample from the needle biopsy is too small for an accurate diagnosis.

Treatment

Treatment has several goals:

·                     Relief of symptoms

·                     Removal of the fluid, air, or blood from the pleural space

·                     Treatment of the underlying condition

Procedures

If large amounts of fluid, air, or blood are not removed from the pleural space, they may cause the lung to collapse.

The surgical procedures used to drain fluid, air, or blood from the pleural space are as follows:

·                     During thoracentesis, a needle or a thin, hollow, plastic tube is inserted through the ribs in the back of the chest into the chest wall. A syringe is attached to draw fluid out of the chest. This procedure can remove more than 6 cups (1.5 litres) of fluid at a time.

·                     When larger amounts of fluid must be removed, a chest tube may be inserted through the chest wall. The doctor injects a local painkiller into the area of the chest wall outside where the fluid is. A plastic tube is then inserted into the chest between two ribs. The tube is connected to a box that suctions the fluid out. A chest x-ray is taken to check the tube’s position.

·                     A chest tube also is used to drain blood and air from the pleural space. This can take several days. The tube is left in place, and the patient usually stays in the hospital during this time.

·                     Sometimes the fluid contains thick pus or blood clots, or it may have formed a hard skin or peel. This makes it harder to drain the fluid. To help break up the pus or blood clots, the doctor may use the chest tube to put certain medicines into the pleural space. These medicines are called fibrinolytics. If the pus or blood clots still do not drain out, surgery may be necessary.

Medications

A couple of medications are used to relieve pleurisy symptoms:

·                     Paracetamol (acetaminophen) or anti-inflammatory agents to control pain and decrease inflammation. Only indomethacin (brand name Indocin) has been studied with respect to relief of pleurisy.

·                     Codeine-based cough syrups to control a cough

There may be a role for the use of corticosteroids (for tuberculous pleurisy), tacrolimus (Prograf) and methotrexate (Trexall, Rheumatrex) in the treatment of pleurisy. Further studies are needed.

Lifestyle changes

The following may be helpful in the management of pleurisy:

·                     Lying on the painful side may be more comfortable

·                     Breathing deeply and coughing to clear mucus as the pain eases. Otherwise, pneumonia may develop.

·                     Getting rest

Treating the cause

Ideally, the treatment of pleurisy is aimed at eliminating the underlying cause of the disease.

·                     If the pleural fluid is infected, treatment involves antibiotics and draining the fluid. If the infection is tuberculosis or from a fungus, treatment involves long-term use of antibiotics or antifungal medicines.

·                     If the fluid is caused by tumors of the pleura, it may build up again quickly after it is drained. Sometimes antitumor medicines will prevent further fluid buildup. If they don’t, the doctor may seal the pleural space. This is called pleurodesis. Pleurodesis involves the drainage of all the fluid out of the chest through a chest tube. A substance is inserted through the chest tube into the pleural space. This substance irritates the surface of the pleura. This causes the two layers of the pleura to squeeze shut so there is no room for more fluid to build up.

Chemotherapy or radiation treatment also may be used to reduce the size of the tumors.

•        If congestive heart failure is causing the fluid buildup, treatment usually includes diuretics and other medicines.

The most common and known treatment for pleurisy is generally to carry on as normal, ibuprofen and amoxicilin being common treatments prescribed by doctors. Milder forms of Pleurisy can be noticed by less inflammatres of the arms and legs. If this is the case Pleurisy will clear of all symptoms within two weeks.

Lung abscess

Lung abscess is necrosis of the pulmonary tissue and formation of cavities (more than 2 cm) containing necrotic debris or fluid caused by microbial infection.

This pus-filled cavity is often caused by aspiration, which may occur during altered consciousness. Alcoholism is the most common condition predisposing to lung abscesses.

Lung abscess is considered primary (60%) when it results from existing lung parenchymal process and is termed secondary when it complicates another process e.g. vascular emboli or follows rupture of extrapulmonary abscess into lung.

Causes

Conditions contributing to lung abscess

•        Aspiration of oropharyngeal or gastric secretion

•        Septic emboli

•        Necrotizing pneumonia

•        Vasculitis: Wegener’s granulomatosis

•        Necrotizing tumors: 8% to 18% are due to neoplasms across all age groups, higher in older people; primary squamous carcinoma of the lung is the most common.

Organisms

In the post-antibiotic era pattern of frequency is changing. In older studies anaerobes were found in up to 90% cases but they are much less frequent now.

•        Anaerobic bacteria: Peptostreptococcus, Bacteroides, Fusobacterium species,

•        Microaerophilic streptococcus : Streptococcus milleri

•        Aerobic bacteria: Staphylococcus, Klebsiella, Haemophilus, Pseudomonas, Nocardia, Escherichia coli, Streptococcus, Mycobacteria

•        Fungi: Candida, Aspergillus

•        Parasites: Entamoeba histolytica,

·                    

·                      

·                     Pathology image of a lung abscess.

 

Signs and symptoms

Onset of symptoms is often gradual, but in necrotizing staphylococcal or gram-negative bacillary pneumonias patients can be acutely ill. Cough, fever with shivering and night sweats are often present. Cough can be productive with foul smelling purulent sputum (≈70%) or less frequently with blood (i.e. hemoptysis in one third cases). Affected individuals may also complain of chest pain, shortness of breath, lethargy and other features of chronic illness.

Patients are generally cachectic at presentation. Finger clubbing is present in one third of patients. Dental decay is common especially in alcoholics and children. On examination of chest there will be features of consolidation such as localised dullness on percussion, bronchial breath sound etc.

 

Lung abscess on X-ray film

 

Lung abscess on CT-scan imagination

 

Abscess is often unilateral and single involving posterior segments of the upper lobes and the apical segments of the lower lobes as these areas are gravity dependent when lying down. Presence of air-fluid levels implies rupture into the bronchial tree or rarely growth of gas forming organism.

Laboratory studies

Raised inflammatory markers (high ESR, CRP) are usual but not specific. Examination of sputum is important in any pulmonary infections and here often reveals mixed flora. Transtracheal of Transbronchial (via bronchoscopy) aspirates can also be cultured. Fibre optic bronchoscopy is often performed to exclude obstructive lesion; it also helps in bronchial drainage of pus.

Management

Broadspectrum antibiotic to cover mixed flora is the mainstay of treatment. Pulmonary physiotherapy and postural drainage are also important. Surgical procedures are required in selective patients for drainage or pulmonary resection.

Complications

Rare nowadays but include spread of infection to other lung segments, bronchiectasis, empyema, and bacteraemia with metastatic infection such as brain abscess

Prognosis

Most cases respond to antibiotic and prognosis is usually excellent unless there is a debilitating underlying condition. Mortality from lung abscess alone is around 5% and is improving.

 

Toxic shock

Toxic shock syndrome (TSS) is a potentially fatal illness caused by a bacterial toxin. Different bacterial toxins may cause toxic shock syndrome, depending on the situation. The causative bacteria include Staphylococcus aureus and Streptococcus pyogenes. Streptococcal TSS is sometimes referred to as toxic shock-like syndrome (TSLS) or streptococcal toxic shock syndrome (STSS).

Signs and symptoms

Symptoms of toxic shock syndrome vary depending on the underlying cause. TSS resulting from infection with the bacterium Staphylococcus aureus typically manifests in otherwise healthy individuals with high fever, accompanied by low blood pressure, malaise and confusion, which can rapidly progress to stupor, coma, and multiple organ failure. The characteristic rash, often seen early in the course of illness, resembles a sunburn, and can involve any region of the body, including the lips, mouth, eyes, palms and soles. In patients who survive the initial phase of the infection, the rash desquamates, or peels off, after 10–14 days.

In contrast, TSS caused by the bacterium Streptococcus pyogenes, or TSLS, typically presents in people with pre-existing skin infections with the bacteria. These individuals often experience severe pain at the site of the skin infection, followed by rapid progression of symptoms as described above for TSS. In contrast to TSS caused by Staphylococcus, streptococcal TSS less often involves a sunburn-like rash.

1.    Body temperature > 38.9 °C (102.02 °F)

2.    Systolic blood pressure < 90 mmHg

3.    Diffuse rash, intense erythroderma, blanching with subsequent desquamation, especially of the palms and soles

4.    Involvement of three or more organ systems:

o     Gastrointestinal (vomiting

, diarrhea)

o     Mucous membrane hyperemia (vaginal, oral, conjunctival)

o     Renal failure (serum creatinine > 2 times normal)

o     Hepatic inflammation (AST, ALT > 2 times normal)

o     Thrombocytopenia (platelet count < 100,000 / mm³)

o     CNS involvement (confusion without any focal neurological findings)

 

 

Pathophysiology

In both TSS (caused by S. aureus) and TSLS (caused by S. pyogenes), disease progression stems from a superantigen toxin that allows the nonspecific binding of MHC II with T cell receptors, resulting in polyclonal T cell activation. In typical T cell recognition, an antigen is taken up by an antigen-presenting cell, processed, expressed on the cell surface in complex with class II major histocompatibility complex (MHC) in a groove formed by the alpha and beta chains of class II MHC, and recognized by an antigen-specific T cell receptor.

By contrast, superantigens do not require processing by antigen-presenting cells but instead interact directly with the invariant region of the class II MHC molecule. In patients with TSS, up to 20% of the body’s T cells can be activated at one time. This polyclonal T-cell population causes a cytokine storm, followed by a multisystem disease. The toxin in S. aureus infections is TSS Toxin-1, or TSST-1. The TSST-1 is secreted as a single polypeptide chain.

The gene encoding toxic shock syndrome toxin is carried by a mobile genetic element of S. aureus in the SaPI family of pathogenicity islands.

Treatment

The severity of this disease frequently warrants hospitalization. Admission to the intensive care unit is ofteecessary for supportive care (for aggressive fluid management, ventilation, renal replacement therapy and inotropic support), particularly in the case of multiple organ failure.The source of infection should be removed or drained if possible: abscesses and collections should be drained. Anyone wearing a tampon at the onset of symptoms should remove it immediately. Outcomes are poorer in patients who do not have the source of infection removed

Antibiotic treatment should cover both S. pyogenes and S. aureus. This may include a combination of cephalosporins, penicillins or vancomycin. The addition of clindamycin or gentamicin reduces toxin production and mortality.

Prognosis

With proper treatment, patients usually recover in two to three weeks. The condition can, however, be fatal within hours.

 

LUNG CANCER

Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary lung cancers, are carcinomas that derive from epithelial cells. The main types of lung cancer are small-cell lung carcinoma (SCLC), also called oat cell cancer, and non-small-cell lung carcinoma (NSCLC). The most common cause of lung cancer is long-term exposure to tobacco smoke, which causes 80–90% of lung cancers. Nonsmokers account for 10–15% of lung cancer cases, and these cases are often attributed to a combination of genetic factors, radon gas, asbestos, and air pollution including secondhand smoke.

The most common symptoms are coughing (including coughing up blood), weight loss and shortness of breath. Lung cancer may be seen on chest radiograph and computed tomography (CT scan). The diagnosis is confirmed with a biopsy. This is usually performed by bronchoscopy or CT-guided biopsy. Treatment and prognosis depend on the histological type of cancer, the stage (degree of spread), and the patient’s general well-being, measured by performance status. Common treatments include surgery, chemotherapy, and radiotherapy. NSCLC is sometimes treated with surgery, whereas SCLC usually responds better to chemotherapy and radiotherapy.

Survival depends on stage, overall health, and other factors. Overall, 15% of people in the United States diagnosed with lung cancer survive five years after the diagnosis. Worldwide, lung cancer is the most common cause of cancer-related death in men and women, and is responsible for 1.38 million deaths annually, as of 2008.

 

Lung cancers are classified according to histological type. This classification has important implications for clinical management and prognosis of the disease. The vast majority of lung cancers are carcinomas—malignancies that arise from epithelial cells. Lung carcinomas are categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope. The two broad classes are non-small-cell and small-cell lung carcinoma.

Non-small-cell lung carcinoma

 

Micrograph of squamous carcinoma, a type of non-small-cell carcinoma, FNA specimen, Pap stain

The three main subtypes of NSCLC are adenocarcinoma, squamous-cell lung carcinoma, and large-cell lung carcinoma.

Nearly 40% of lung cancers are adenocarcinoma, which usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have smoked fewer than 100 cigarettes in their lifetimes (“never-smokers”), adenocarcinoma is the most common form of lung cancer. A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have different responses to treatment.

Squamous-cell carcinoma accounts for about 30% of lung cancers. They typically occur close to large airways. A hollow cavity and associated necrosis are commonly found at the center of the tumor.

About 9% of lung cancers are large-cell carcinoma. These are so named because the cancer cells are large, with excess cytoplasm, large nuclei and conspicuous nucleoli.

Small-cell lung carcinoma

 

Small-cell lung carcinoma (microscopic view of a core needle biopsy)

In small-cell lung carcinoma (SCLC), the cells contain dense neurosecretory granules (vesicles containing neuroendocrine hormones), which give this tumor an endocrine/paraneoplastic syndrome association. Most cases arise in the larger airways (primary and secondary bronchi). These cancers grow quickly and spread early in the course of the disease. Sixty to seventy percent have metastatic disease at presentation. This type of lung cancer is strongly associated with smoking.

Others

Four main histological subtypes are recognized, although some cancers may contain a combination of different subtypes. Rare subtypes include glandular tumors, carcinoid tumors, and undifferentiated carcinomas.

Metastasis

The lung is a common place for metastasis of tumors from other parts of the body. Secondary cancers are classified by the site of origin; e.g., breast cancer that has spread to the lung is called metastatic breast cancer. Metastases often have a characteristic round appearance on chest radiograph.

Primary lung cancers themselves most commonly metastasize to the brain, bones, liver, and adrenal glands. Immunostaining of a biopsy is often helpful to determine the original source.

Signs and symptoms

Symptoms and signs that may suggest lung cancer include:

•      coughing

•      weight loss

•      dyspnea (shortness of breath)

•      chest pain

•      hemoptysis (coughing up blood)

•      bone pain

•      clubbing of the fingernails

•      fever

•      fatigue

•      superior vena cava obstruction

•      dysphagia (difficulty swallowing)

•      wheezing

If the cancer grows in the airway, it may obstruct airflow, causing breathing difficulties. The obstruction can lead to accumulation of secretions behind the blockage, and predispose to pneumonia.

Depending on the type of tumor, so-called paraneoplastic phenomena may initially attract attention to the disease. In lung cancer, these phenomena may include Lambert–Eaton myasthenic syndrome (muscle weakness due to autoantibodies), hypercalcemia, or syndrome of inappropriate antidiuretic hormone (SIADH). Tumors in the top (apex) of the lung, known as Pancoast tumors, may invade the local part of the sympathetic nervous system, leading to Horner’s syndrome, as well as damage to the brachial plexus.

Many of the symptoms of lung cancer (poor appetite, weight loss, fever, fatigue) are not specific. In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis include the brain, bone, adrenal glands, contralateral (opposite) lung, liver, pericardium, and kidneys. About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiograph.

Causes

Cancer develops following genetic damage to DNA. This genetic damage affects the normal functions of the cell, including cell proliferation, programmed cell death (apoptosis) and DNA repair. As more damage accumulates, the risk of cancer increases.

Smoking

Cross section of a human lung: The white area in the upper lobe is cancer; the black areas are discoloration due to smoking.

Smoking, particularly of cigarettes, is by far the main contributor to lung cancer. Cigarette smoke contains over 60 known carcinogens, including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue. Across the developed world, 90% of lung cancer deaths in men during the year 2000 were attributed to smoking (70% for women). Smoking accounts for 80–90% of lung cancer cases

Passive smoking—the inhalation of smoke from another’s smoking—is a cause of lung cancer in nonsmokers. A passive smoker can be classified as someone living or working with a smoker. Studies from the US, Europe, the UK, and Australia have consistently shown a significantly increased risk among those exposed to passive smoke. Those who live with someone who smokes have a 20–30% increase in risk while those who work in an environment with second hand smoke have a 16–19% increase in risk. Investigations of sidestream smoke suggest it is more dangerous than direct smoke. Passive smoking causes about 3,400 deaths from lung cancer each year in the USA

Radon gas

Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the Earth’s crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon is the second-most common cause of lung cancer in the USA, after smoking. The risk increases 8–16% for every 100 Bq/m³ increase in the radon concentration. Radon gas levels vary by locality and the composition of the underlying soil and rocks. For example, in areas such as Cornwall in the UK (which has granite as substrata), radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. The United States Environmental Protection Agency (EPA) estimates one in 15 homes in the US has radon levels above the recommended guideline of 4 picocuries per liter (pCi/l) (148 Bq/m³).

Asbestos

Asbestos can cause a variety of lung diseases, including lung cancer. Tobacco smoking and asbestos have a synergistic effect on the formation of lung cancer. Asbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).

Air pollution

Outdoor air pollution has a small effect on increasing the risk of lung cancer. Fine particulates (PM_2.5) and sulfate aerosols, which may be released in traffic exhaust fumes, are associated with slightly increased risk. For nitrogen dioxide, an incremental increase of 10 parts per billion increases the risk of lung cancer by 14%. Outdoor air pollution is estimated to account for 1–2% of lung cancers.

Genetics

Some people have a genetic predisposition to lung cancer. In relatives of people with lung cancer, the risk is increased 2.4 times. This may be due to genetic polymorphisms.

Other causes

Numerous other substances, occupations, and environmental exposures have been linked to the genesis of cancer in lung tissue of humans. In its List of Classifications by Cancer Sites, the International Agency for Research on Lung Cancer (IARC) states there is “sufficient evidence” to show the following are carcinogenic in lung:

•      Aluminum production

•      Arsenic and inorganic arsenic compounds

•      Beryllium and beryllium compounds

•      Bis-(chloromethyl) ether

•      Methyl ether (technical grade)

•      Cadmium and cadmium compounds

•      Chromium(VI) compounds

•      Coal (indoor emissions from household coal burning)

•      Combustion (incomplete)

•      Coal gasification

•      Coal-tar pitch

•      Coke production

•      Diesel engine exhaust

•      Gamma radiation

•      Hematite mining (underground)

•      Iron and steel founding

•      MOPP (vincristine-prednisone-nitrogen mustard-procarbazine mixture)

•      Nickel compounds

•      Painting

•      Plutonium

•      Radon-222 and its decay products

•      Rubber production industry

•      Silica dust (crystalline)

•      Soot

•      Sulfur mustard

•      X-radiation

Pathogenesis

Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes. Oncogenes are believed to make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens. Mutations in the K-ras proto-oncogene are responsible for 10–30% of lung adenocarcinomas. The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion.^[ Mutations and amplification of EGFR are common in non-small-cell lung cancer and provide the basis for treatment with EGFR-inhibitors. Her2/neu is affected less frequently.Chromosomal  damage can lead to loss of heterozygosity. This can cause inactivation of tumor suppressor genes. Damage to chromosomes 3p, 5q, 13q, and 17p are particularly common in small-cell lung carcinoma. The p53 tumor suppressor gene, located on chromosome 17p, is affected in 60-75% of cases.

Diagnosis

 

Chest radiograph showing a cancerous tumor in the left lung

Performing a chest radiograph is one of the first investigative steps if a patient reports symptoms that may suggest lung cancer. This may reveal an obvious mass, widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (collapse), consolidation (pneumonia), or pleural effusion. CT imaging is typically used to provide more information about the type and extent of disease. Bronchoscopy or CT-guided biopsy is often used to sample the tumor for histopathology.

 

CT scan showing a cancerous tumor in the left lung

Lung cancer often appears as a solitary pulmonary nodule on a chest radiograph. However, the differential diagnosis is wide. Many other diseases can also give this appearance, including tuberculosis, fungal infections, metastatic cancer, or organizing pneumonia. Less common causes of a solitary pulmonary nodule include hamartomas, bronchogenic cysts, adenomas, arteriovenous malformation, pulmonary sequestration, rheumatoid nodules, Wegener’s granulomatosis, or lymphoma. Lung cancer can also be an incidental finding, as a solitary pulmonary nodule on a chest radiograph or CT scan taken for an unrelated reason. The definitive diagnosis of lung cancer is based on histological examination of the suspicious tissue in the context of the clinical and radiological features.

Staging

Lung cancer staging is an assessment of the degree of spread of the cancer from its original source. It is one of the factors affecting the prognosis and potential treatment of lung cancer.

The initial evaluation of non-small-cell lung cancer (NSCLC) staging uses the TNM classification. This based on the size of the primary tumor, lymph node involvement, and distant metastasis. After this, using the TNM descriptors, a group is assigned, ranging from occult cancer, through stages 0, IA (one-A), IB, IIA, IIB, IIIA, IIIB and IV (four). This stage group assists with the choice of treatment and estimate of prognosis. Small-cell lung carcinoma (SCLC) has traditionally been classified as ‘limited stage’ (confined to one half of the chest and within the scope of a single tolerable radiotherapy field) or ‘extensive stage’ (more widespread disease). However, the TNM classification and grouping are useful in estimating prognosis.

For both NSCLC and SCLC, the two general types of staging evaluations are clinical staging and surgical staging. Clinical staging is performed prior to definitive surgery. It is based on the results of imaging studies (such as CT scans and PET scans) and biopsy results. Surgical staging is evaluated either intra- or postoperatively, and is based on the combined results of surgical and clinical findings, including surgical sampling of thoracic lymph nodes.

Prevention

Prevention is the most cost-effective means of mitigating lung cancer development. While in most countries, industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventive tool in this process.

Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries. Bhutan has had a complete smoking ban since 2005. India introduced a ban on smoking in public in October 2008.

The World Health Organization has called for governments to institute a total ban on tobacco advertising to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by 16% where instituted

The long-term use of supplemental vitamin A, vitamin C, vitamin D or vitamin E does not reduce the risk of lung cancer. Some studies suggest people who eat diets with a higher proportion of vegetables and fruit tend have a lower risk, but this is likely due to confounding. More rigorous studies have not demonstrated a clear association.

Screening

Screening refers to the use of medical tests to detect disease in asymptomatic people. Possible screening tests for lung cancer include sputum cytology, chest radiograph (CXR), and computed tomography (CT). Screening programs using CXR or cytology have not demonstrated any benefit. Screening those at high risk (i.e. age 55 to 79 who have smoked more than 30 pack years or those who have had previous lung cancer) annually with low-dose CT scans may reduce the chance of death from lung cancer by an absolute amount of 0.3% (relative amount of 20%).The potential risks of screening however are not well known.

Treatment

Treatment for lung cancer depends on the cancer’s specific cell type, how far it has spread, and the patient’s performance status. Common treatments include palliative care, surgery, chemotherapy, and radiation therapy.

Surgery

Pneumonectomy specimen containing a squamous-cell carcinoma, seen as a white area near the bronchi

If investigations confirm NSCLC, the stage must be reassessed to determine whether the disease is localized and amenable to surgery or whether it has spread to the point where it cannot be cured surgically. CT scan and positron emission tomography (PET) are used. If mediastinal lymph node involvement is suspected, mediastinoscopy may be used to sample the nodes and assist staging.

Blood tests and pulmonary function testing are also necessary to assess whether the patient is well enough for surgery. If pulmonary function tests reveal poor respiratory reserve, surgery may be contraindicated.

In most cases of early-stage NSCLC, removal of a lobe of lung (lobectomy) is the surgical treatment of choice. In patients who are unfit for a full lobectomy, a smaller sublobar excision (wedge resection) may be performed. However, wedge resection has a higher risk of recurrent disease than lobectomy. Radioactive iodine brachytherapy at the margins of wedge excision may reduce the risk of recurrence. Rarely, removal of a whole lung (pneumonectomy) is performed.

Video-assisted thoracoscopic surgery and VATS lobectomy use a minimally invasive approach to lung cancer surgery. VATS lobectomy is equally effective compared to conventional open lobectomy, and with less postoperative illness.

In SCLC, chemotherapy and/or radiotherapy is typically used However the role of surgery in SCLC is being reconsidered. Surgery might improve outcomes when added to chemotherapy and radiation in early stage SCLC.

Radiotherapy

Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients with NSCLC who are not eligible for surgery. This form of high-intensity radiotherapy is called radical radiotherapy. A refinement of this technique is continuous hyperfractionated accelerated radiotherapy (CHART), in which a high dose of radiotherapy is given in a short time period. Postoperative thoracic radiotherapy generally should not be used after curative intent surgery for NSCLC. Some patients with mediastinal N2 lymph node involvement might benefit from post-operative radiotherapy.

For potentially curable SCLC cases, chest radiotherapy is often recommended in addition to chemotherapy.

If cancer growth blocks a short section of bronchus, brachytherapy (localized radiotherapy) may be given directly inside the airway to open the passage. Compared to external beam radiotherapy, brachytherapy allows a reduction in treatment time and reduced radiation exposure to healthcare staff.

Prophylactic cranial irradiation (PCI) is a type of radiotherapy to the brain, used to reduce the risk of metastasis. PCI is most useful in SCLC. In limited-stage disease, PCI increases three-year survival from 15% to 20%; in extensive disease, one-year survival increases from 13% to 27%.

Recent improvements in targeting and imaging have led to the development of stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiotherapy, high doses are delivered in a small number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical comorbidities

For both NSCLC and SCLC patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy)

 

Chemotherapy

The chemotherapy regimen depends on the tumor type.

SMALL-CELL LUNG CARCINOMA

Even if relatively early stage, SCLC is treated primarily with chemotherapy and radiation. In SCLC, cisplatin and etoposide are most commonly used. Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, and irinotecan are also usedNon-small cell lung carcinoma

In advanced NSCLC, chemotherapy improves survival and is used as first-line treatment, provided the patient is well enough for the treatment Typically, two drugs are used, of which one is often platinum-based (either cisplatin or carboplatin). Other commonly used drugs are gemcitabine, paclitaxel, docetaxel pemetrexed, etoposide or vinorelbine.

ADJUVANT CHEMOTHERAPY

Adjuvant chemotherapy refers to the use of chemotherapy after apparently curative surgery to improve the outcome. In NSCLC, samples are taken of nearby lymph nodes during surgery to assist staging. If stage II or III disease is confirmed, adjuvant chemotherapy improves survival by 5% at five years. The combination of vinorelbine and cisplatin is more effective than older regimens.

Adjuvant chemotherapy for patients with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit. Trials of preoperative chemotherapy (neoadjuvant chemotherapy) in resectable NSCLC have been inconclusive.

Palliative care

In patients with terminal disease, palliative care or hospice management may be appropriate. These approaches allow additional discussion of treatment options and provide opportunities to arrive at well-considered decisions and may avoid unhelpful but expensive care at the end of life.

Chemotherapy may be combined with palliative care in the treatment of the NSCLC. In advanced cases, appropriate chemotherapy improves average survival over supportive care alone, as well as improving quality of life. With adequate physical fitness, maintaining chemotherapy during lung cancer palliation offers 1.5 to 3 months of prolongation of survival, symptomatic relief, and an improvement in quality of life, with better results seen with modern agents. The NSCLC Meta-Analyses Collaborative Group recommends if the recipient wants and can tolerate treatment, then chemotherapy should be considered in advanced NSCLC.

Prognosis

Prognostic factors in NSCLC include presence or absence of pulmonary symptoms, tumor size, cell type (histology), degree of spread (stage) and metastases to multiple lymph nodes, and vascular invasion. For patients with inoperable disease, prognosis is adversely affected by poor performance status and weight loss of more than 10%. Prognostic factors in small cell lung cancer include performance status, gender, stage of disease, and involvement of the central nervous system or liver at the time of diagnosis.

Prognosis is generally poor. Of all patients with lung cancer, 15% survive for five years after diagnosis. Stage is often advanced at the time of diagnosis. At presentation, 30–40% of cases of NSCLC are stage IV, and 60% of SCLC are stage IV.

For NSCLC, the best prognosis is achieved with complete surgical resection of stage IA disease, with up to 70% five-year survival. For SCLC, the overall five-year survival for patients is about 5%. Patients with extensive-stage SCLC have an average five-year survival rate of less than 1%. The median survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%.

According to data provided by the National Cancer Institute, the median age at diagnosis of lung cancer in the United States is 70 years, and the median age at death is 72 years. In the US, people with medical insurance are more likely to have a better outcome.

Worldwide, lung cancer is the most common cancer in terms of both incidence and mortality. In 2008, there were 1.61 millioew cases, and 1.38 million deaths due to lung cancer. The highest rates are in Europe and North America. The population segment most likely to develop lung cancer is people over 50 who have a history of smoking. In contrast to the mortality rate in men, which began declining more than 20 years ago, women’s lung cancer mortality rates have been rising over the last decades, and are just recently beginning to stabilize. In the USA, the lifetime risk of developing lung cancer is 8% in men and 6% in women.

For every 3–4 million cigarettes smoked, one lung cancer death occurs. The influence of “Big Tobacco” plays a significant role in the smoking culture. Young nonsmokers who see tobacco advertisements are more likely to take up smoking.

The role of passive smoking is increasingly being recognized as a risk factor for lung cancer, leading to policy interventions to decrease undesired exposure of nonsmokers to others’ tobacco smoke. Emissions from automobiles, factories, and power plants also pose potential risks

Eastern Europe has the highest lung cancer mortality among men, while northern Europe and the US have the highest mortality among women. In the United States, black men and women have a higher incidence. Lung cancer incidence is currently less common in developing countries. With increased smoking in developing countries, the incidence is expected to increase in the next few years, notably in China and India

From the 1960s, the incidence of lung adenocarcinoma started to rise relative to other types of lung cancer. This is partly due to the introduction of filter cigarettes. The use of filters removes larger particles from tobacco smoke, thus reducing deposition in larger airways. However, the smoker has to inhale more deeply to receive the same amount of nicotine, increasing particle deposition in small airways where adenocarcinoma tends to arise. The incidence of lung adenocarcinoma continues to rise.