Pneumonia

Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs (alveoli)—associated with fever, chest symptoms, and a lack of air space (consolidation) on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes. Infectious agents include: bacteria, viruses, fungi, and parasites.

Typical symptoms include cough, chest pain, fever, and difficulty breathing. Diagnostic tools include x-rays and examination of the sputum. Vaccines to prevent certain types of pneumonia are available. Treatment depends on the underlying cause with presumed bacterial pneumonia being treated with antibiotics.

Although pneumonia was regarded by William Osler in the 19th century as "the captain of the men of death", the advent of antibiotic therapy and vaccines in the 20th century have seen radical improvements in survival outcomes. Nevertheless, in the third world, and among the very old, the very young and the chronically ill, pneumonia remains a leading cause of death.

Classification
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 can be classified in several ways. It is most commonly classified by where or how it was acquired (community-acquired, aspiration, healthcare-associated, hospital-acquired, and ventilator-associated pneumonia), but 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.

Signs and symptoms
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, confusion, and an increased respiratory rate. In the elderly, confusion may be the most prominent symptom. The typical symptoms in children under five are fever, cough, and fast or difficult breathing. Fever, however, is not very specific, as it occurs in many other common illnesses, and may be absent in those with severe disease or malnutrition. Additionally, a cough is frequently absent in children less than 2 months old. More severe symptoms may include: central cyanosis, decreased thirst, convulsions, persistent vomiting, or a decreased level of consciousness.

Some causes of pneumonia are associated with classic, but non-specific, clinical characteristics. Pneumonia caused by Legionella may occur with abdominal pain, diarrhea, 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".

Physical examination may sometimes reveal low blood pressure, a high heart rate, or a low oxygen saturation. 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. Rales (or crackles) 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. Struggling to breathe, confusion, and blue-tinged skin are signs of a medical emergency.

Cause
Pneumonia is primarily due to infections, with less common causes including irritants and the unknown. Although more than one hundred strains of micro organisms can cause pneumonia, only a few are responsible for most cases. The most common types of infectious are viruses and bacteria with it being less commonly due to fungi or parasites. Mixed infections with both viruses and bacterial may occur in up to 45% of infections in children and 15% of infections in adults. A causative agent is not isolated in approximately half of cases despite careful testing. The term pneumonia is sometimes more broadly applied to inflammation of the lung (for example caused by autoimmune disease, chemical burns or drug reactions), however this is more accurately referred to as pneumonitis.

Bacteria


Bacteria are the most common cause of community acquired pneumonia, with Streptococcus pneumoniae isolated in nearly 50% of cases. Other commonly isolated bacteria include: Haemophilus influenzae in 20%, Chlamydophila pneumoniae in 13%, Mycoplasma pneumoniae in 3%,, Staphylococcus aureus, Moraxella catarrhalis, Legionella pneumophila and gram-negative bacilli.

Risk factors for infection depend on the organism involved. Alcoholism is associated with Streptococcus pneumoniae, anaerobic organisms, and Mycobacterium tuberculosis, smoking is associated with Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Legionella pneumophila, exposure to bird with Chlamydia psittaci, farm animals with Coxiella burnetti, aspiration of stomach contents with anaerobes, and cystic fibrosis with Pseudomonas aeruginosa and Staphylococcus aureus. Streptococcus pneumoniae is more common in the winter.

Viruses
In adults viruses account for approximately a third of pneumonia cases. Commonly implicated agents include: rhinoviruses, coronaviruses, influenza virus, respiratory syncytial virus (RSV), adenovirus, andparainfluenza. Herpes simplex virus is a rare cause of pneumonia, except in newborns. People with weakened immune systems are at increased risk of pneumonia caused by cytomegalovirus (CMV).

Fungi
Fungal pneumonia is uncommon, but it may occur in individuals with weakened immune systems due to AIDS, immunosuppressive drugs, or other medical problems. The pathophysiology of pneumonia caused by fungi is similar to that of bacterial pneumonia. Fungal pneumonia is most often caused by Histoplasma capsulatum, blastomyces, Cryptococcus neoformans, Pneumocystis jiroveci, and Coccidioides immitis. Histoplasmosis is most common in the Mississippi River basin, and coccidioidomycosis is most common in the southwestern United States.

Parasites
A variety of parasites can affect the lungs. These parasites typically enter the body through the skin or the mouth. Once inside the body, they travel to the lungs, usually through the blood. In parasitic pneumonia, as with other kinds of pneumonia, a combination of cellular destruction and immune response causes disruption of oxygen transportation. One type of white blood cell, the eosinophil, responds vigorously to parasite infection. Eosinophils in the lungs can lead to eosinophilic pneumonia, thus complicating the underlying parasitic pneumonia. The most common parasites causing pneumonia are Toxoplasma gondii, Strongyloides stercoralis, and Ascariasis.

Idiopathic
Idiopathic interstitial pneumonia or noninfectious pneumonia are a class of diffuse lung diseases. They include: diffuse alveolar damage, organizing pneumonia, nonspecific interstitial pneumonia, lymphocytic interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, and usual interstitial pneumonia.

Viral
Viruses invade cells in order to reproduce. Typically, a virus reaches the lungs when airborne droplets are inhaled through the mouth or nose. Once in the lungs, the virus invades the cells lining the airways and alveoli. This invasion often leads to cell death, either from damage to the cell by the virus, or from a protective process called apoptosis in which the infected cell destroys itself before it can be used as a conduit for virus reproduction. When the immune system responds to the viral infection, even more lung damage occurs. White blood cells, mainly lymphocytes, activate certain chemical cytokines which allow fluid to leak into the alveoli. This combination of cell destruction and fluid-filled alveoli interrupts the normal transportation of oxygen into the bloodstream.

As well as damaging the lungs, many viruses affect other organs and thus disrupt many body functions. Viruses can also make the body more susceptible to other bacterial infections; in this way bacterial pneumonia can arrise as a co-morbid condition.

Bacterial
Bacteria typically enter the lung when airborne droplets are inhaled, but can also reach the lung through the bloodstream when there is an infection in another part of the body. Many bacteria live in parts of the upper respiratory tract, such as the nose, mouth and sinuses, and can easily be inhaled into the alveoli. Once inside, bacteria may invade the spaces between cells and between alveoli through connecting pores. This invasion triggers the immune system to send neutrophils, a type of defensive white blood cell, to the lungs. The neutrophils engulf and kill the offending organisms, and also release cytokines, causing a general activation of the immune system. This leads to the fever, chills, and fatigue common in bacterial and fungal pneumonia. The neutrophils, bacteria, and fluid from surrounding blood vessels fill the alveoli and interrupt normal oxygen transportation.

Diagnosis
Pneumonia is typically diagnosed based on a combination of physical signs and a chest X-ray. Confirming the underlying cause can be difficult, however, with no definitive test able to distinguish between bacterial and not-bacterial origin. The World Health Organization has defined pneumonia in children clinically based on a either a cough or difficulty breathing and a rapid respiratory rate, chest indrawing, or a decreased level of consciousness. A rapid respiratory rate is defined as greater than 60 breaths per minute in children under 2 months old, 50 breaths per minute in children two months to one year old, or greater than 40 breaths per minute in children one to five years old. In children, an increased respiratory rate and lower chest indrawing are more sensitive than hearing chest crackles with a stethoscope.

In adults investigations are generally not needed in mild cases as if all vital signs and auscultation are normal the risk the risk of pneumonia is very low. In those requiring admission to a hospital, pulse oximetry, chest radiography, and blood tests including a complete blood count, serum electrolytes, C-reactive protein, and possibly liver function tests are recommended. The diagnosis of influenza-like illness can be made based on presenting signs and symptoms however verification of an influenza infection requires testing. Thus treatment is frequently based on the presence of influenza in the community or a rapid influenza test.

Imaging
A chest radiograph is frequently used in diagnosis. In people with mild disease imaging is only needed 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 severity of disease and do not reliably distinguish between bacterial versus viral infection.

X-ray signs of bacterial community acquired pneumonia classically show lung consolidation of one lung segmental lobe. However, radiographic findings may be variable, especially 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 cases may appear normal, hyper-inflated, have bilateral patchy areas, or present similar to bacterial pneumonia with lobar consolidation. A CT scan can give additional information in indeterminate cases.

Microbiology
For people managed in the community figuring out the causative agent is not cost effective, and typically does not alter management. For those who do not respond to treatment, sputum culture should be considered, and culture for Mycobacterium tuberculosis should be carried out in those 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. Viral infections can be confirmed via detection of either the virus or its antigens with culture or polymerase chain reaction (PCR) among other techniques. With routine microbiological testing a causative agent is determined in only 15% of cases.

Differential diagnosis
Several diseases can present similar to pneumonia, including: 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.

Prevention
Prevention includes vaccination, environmental measures, and appropriately treating other diseases.

Vaccination
Vaccination is effective for preventing certain bacterial and viral pneumonias in both children and adults.

Influenza vaccines are modestly effective against influenza A and B. The Center for Disease Control and Prevention (CDC) recommends that everyone 6 months and older get yearly vaccination. When an influenza outbreak is occurring, medications such as amantadine, rimantadine, zanamivir, and oseltamivir can help prevent influenza.

Vaccinations against Haemophilus influenzae and Streptococcus pneumoniae in the first year of life have greatly reduced the role these bacteria play in causing pneumonia in children. Vaccinating children against Streptococcus pneumoniae has also led to a decreased incidence of these infections in adults, because many adults acquire infections from children. Hib vaccine is now widely used around the globe. A vaccine against Streptococcus pneumoniae is also available for adults, and has been found to decrease the risk of invasive pneumococcal disease.

Environmental
Reducing indoor air pollution is recommended as is smoking cessation.

Other
Appropriately treating underlying illnesses (such as AIDS) can decrease a person's risk of pneumonia.

There are several ways to prevent pneumonia in newborn infants. Testing pregnant women for Group B Streptococcus and Chlamydia trachomatis, and giving antibiotic treatment, if needed, reduces pneumonia in infants. Suctioning the mouth and throat of infants with meconium-stained amniotic fluid decreases the rate of aspiration pneumonia.

Management
Typically, oral antibiotics, rest, simple analgesics, and fluids are sufficient 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 22–42% 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 saturation's of less than 90% should be hospitalized. The utility of chest physiotherapy in pneumonia has not yet been determined. Over the counter cough medicine has not been found to be effective.

Bacterial
Antibiotics improve outcomes in those with bacterial pneumonia. Initially antibiotic choice depends 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 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), and doxycycline have displaced amoxicillin as first-line outpatient treatment in adults. In children with mild or moderate symptoms amoxicillin is still the first line. The use of fluoroquinolones in uncomplicated cases is discouraged due to concerns of side effects and resistance. The duration of treatment has traditionally been seven to ten days, but there is increasing evidence that short courses (three to five days) are similarly effective. Antibiotics recommended for hospital-acquired pneumonia include third- and fourth-generation cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and vancomycin. These antibiotics are often given intravenously, and may be used in combination.

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. 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. The use of corticosteroids is controversial.

Aspiration
Aspiration pneumonitis is generally treated conservatively with antibiotics only indicated 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 commonly used in aspiration pneumonia, but there is no evidence to support their effectiveness.

Prognosis
With treatment, most types of bacterial pneumonia can be cleared within two to four weeks and mortality is very low. Viral pneumonia may last longer, and mycoplasmal pneumonia may take four to six weeks to resolve completely. The eventual outcome of an episode of pneumonia depends on how ill the person is when he or she was first diagnosed. Before the advent of antibiotics mortality was typically 30% for hospitalized patients.

In the United States, about 5% of those diagnosed with pneumococcal pneumonia will die. In cases where the pneumonia progresses to blood infection, just over 20% will die.

The death rate (or mortality) also depends on the underlying cause of the pneumonia. Pneumonia caused by Mycoplasma, for instance, is associated with lower mortality. However, about half of the people who develop methicillin-resistant Staphylococcus aureus (MRSA) pneumonia while on a ventilator will die. In regions of the world without advanced health care systems, pneumonia is even more deadly. Limited access to clinics and hospitals, limited access to x-rays, limited antibiotic choices, and inability to diagnose and treat underlying conditions inevitably lead to higher rates of death from pneumonia. For these reasons, the majority of deaths in children under five due to pneumococcal disease occur in developing countries.

Adenovirus can cause severe necrotizing pneumonia in which all or part of a lung has increased translucency radiographically, which is called Swyer-James Syndrome. Severe adenovirus pneumonia also may result in bronchiolitis obliterans, a subacute inflammatory process in which the small airways are replaced by scar tissue, resulting in a reduction in lung volume and lung compliance. Sometimes pneumonia can lead to additional complications. Complications are more frequently associated with bacterial pneumonia than with viral pneumonia. The most important complications include respiratory and circulatory failure and pleural effusions, empyema or abscesses.

Clinical prediction rules
Clinical prediction rules have been developed to more objectively prognosticate outcomes in pneumonia. Although these rules are often used in deciding whether or not to hospitalize the person, they were derived simply to inform on prognosis; neither index was designed or tested as guide to determine whether the person would benefit by hospital admission.
 * Pneumonia severity index (or PORT Score) – online calculator
 * CURB-65 score, which takes into account the severity of symptoms, any underlying diseases, and age – online calculator

Pleural effusion, empyema, and abscess


In pneumonia, a collection of fluid (pleural effusion) often forms in the space that surrounds the lung (the pleural cavity). Occasionally, microorganisms will infect this fluid, causing what is called an empyema. To distinguish an empyema from the more common simple parapneumonic effusion, the fluid is collected with a needle (thoracentesis), and examined. If this shows evidence of empyema, complete drainage of the fluid may be necessary, often requiring a chest tube. 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 need only be drained 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 or chest CT scan. Abscesses typically occur in aspiration pneumonia, and often contain several types of bacteria. 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
Because pneumonia affects the lungs, people with pneumonia often have difficulty breathing, sometimes to the point where mechanical assistance is required. Non-invasive breathing assistance may be helpful, such as with a bi-level positive airway pressure machine. In other cases, placement of an endotracheal tube (breathing tube) may be necessary, and a ventilator may be used to help the person breathe.

Pneumonia can also 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 very stiff. This stiffness, combined with severe difficulties extracting oxygen due to the alveolar fluid, creates a need for mechanical ventilation.

Sepsis and septic shock are potential complications of pneumonia. Sepsis occurs when microorganisms enter the bloodstream and the immune system responds by secreting cytokines. Sepsis most often occurs with bacterial pneumonia; Streptococcus pneumoniae is the most common cause. Individuals with sepsis or septic shock need hospitalization in an intensive care unit. They often require intravenous fluids and medications to help keep their blood pressure up. Sepsis can cause liver, kidney, and heart damage, among other problems, and it is often fatal.

Epidemiology
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Pneumonia is a common illness affecting approximately 450 million people a year and occurring in all parts of the world. It is a major cause of death among all age groups resulting in 4 million deaths (7% of the world's yearly total). Rates are greatest in children less than five, and adults older than 75 years of age. It occurs about five times more frequently in the developing world versus the developed world. Viral pneumonia accounts for about 200 million cases.

Children
In 2008 pneumonia occurred in approximately 156 million children (151 million in the developing world and 5 million in the developed world). It resulted in 1.6 million deaths, or 28–34% of all deaths in those under five years of age, of which 95% occurred in the developing world. Countries with the greatest burden of disease include: India (43 million), China (21 million) and Pakistan (10 million). It is the leading cause of death among children in low income countries. Many of these deaths occur in the newborn period. The World Health Organization estimates that one in three newborn infant deaths are due to pneumonia. Approximately half of these deaths are theoretically preventable, as they are caused by the bacteria for which an effective vaccine is available.

History


Pneumonia has been a common disease throughout human history. The symptoms were described by Hippocrates (c. 460 BC – 370 BC): "Peripneumonia, and pleuritic affections, are to be thus observed: If the fever be acute, and if there be pains on either side, or in both, and if expiration be if cough be present, and the sputa expectorated be of a blond or livid color, or likewise thin, frothy, and florid, or having any other character different from the common... When pneumonia is at its height, the case is beyond remedy if he is not purged, and it is bad if he has dyspnoea, and urine that is thin and acrid, and if sweats come out about the neck and head, for such sweats are bad, as proceeding from the suffocation, rales, and the violence of the disease which is obtaining the upper hand." However, Hippocrates referred to pneumonia as a disease "named by the ancients." He also reported the results of surgical drainage of empyemas. Maimonides (1135–1204 AD) observed "The basic symptoms which occur in pneumonia and which are never lacking are as follows: acute fever, sticking [pleuritic] pain in the side, short rapid breaths, serrated pulse and cough." This clinical description is quite similar to those found in modern textbooks, and it reflected the extent of medical knowledge through the Middle Ages into the 19th century.

Bacteria were first seen in the airways of individuals who died from pneumonia by Edwin Klebs in 1875. Initial work identifying the two common bacterial causes Streptococcus pneumoniae and Klebsiella pneumoniae was performed by Carl Friedländer and Albert Fränkel in 1882 and 1884, respectively. Friedländer's initial work introduced the Gram stain, a fundamental laboratory test still used today to identify and categorize bacteria. Christian Gram's paper describing the procedure in 1884 helped differentiate the two different bacteria, and showed that pneumonia could be caused by more than one microorganism.

Sir William Osler, known as "the father of modern medicine," appreciated the death and disability cause by pneumonia, describing it as the "captain of the men of death" in 1918, as it had overtaken tuberculosis as one of the leading causes of death in this time. This phrase was originally coined by John Bunyan in reference to "consumption" (tuberculosis). Osler also described pneumonia as "the old man's friend" as death was often quick and painless when there was many slower more painful ways to die.

Several developments in the 1900s improved the outcome for those with pneumonia. With the advent of penicillin and other antibiotics, modern surgical techniques, and intensive care in the twentieth century, mortality from pneumonia, which had approached 30%, dropped precipitously in the developed world. Vaccination of infants against Haemophilus influenzae type B began in 1988 and led to a dramatic decline in cases shortly thereafter. Vaccination against Streptococcus pneumoniae in adults began in 1977, and in children in 2000, resulting in a similar decline.

Society and culture
Because of the combination of a very high burden of disease in developing countries and a relatively low awareness of the disease in industrialized countries, the global health community has declared November 12 to be World Pneumonia Day, a day for concerned citizens and policy makers to take action against the disease.