Pneumonia In-Depth

Introduction

Pneumonia is an inflammation of the lung that is most often caused by infection with bacteria, viruses, or other organisms. Occasionally, inhaled chemicals that irritate the lungs can cause pneumonia. Healthy people can usually fight off pneumonia infections. However, people who are sick, including those who are recovering from the flu (influenza) or an upper respiratory illness, have weakened immune systems that make it easier for bacteria to grow in their lungs.

When air is inhaled through the nose or mouth, it travels down the trachea to the bronchus, where it first enters the lung. From the bronchus, air goes through the bronchi, into the even smaller bronchioles and lastly into the alveoli.

Defining Pneumonia by Location in the Lung

Pneumonia may be defined according to its location in the lung:

• Lobar Pneumonia occurs in one part, or lobe, of the lung.
• Bronchopneumonia tends to be scattered throughout the lung.

Defining Pneumonia by Origin of Infection

Doctors often classify pneumonia based on where you contracted the disease. This also helps predict which organisms are most likely responsible for the illness and, therefore, helps decide treatment.

Community-Acquired Pneumonia (CAP). People with this type of pneumonia contracted the infection outside a hospital setting. It is one of the most common infectious diseases. The disease often follows a viral respiratory infection such as the flu.

One of the most common causes of bacterial CAP is Streptococcus pneumoniae. Other causes include Haemophilus influenzae, mycoplasma, and Chlamydia.

Hospital-Acquired Pneumonia. Hospital-acquired pneumonia is an infection of the lungs contracted during a hospital stay. This type of pneumonia tends to be more serious because hospital patients already have weakened defense mechanisms and the infecting organisms are usually more dangerous than those encountered in the community. Hospital patients are particularly vulnerable to gram-negative bacteria and staphylococci. Hospital-acquired pneumonia is also called nosocomial pneumonia.

Click the icon to see an image of hospital-acquired pneumonia.

Disease Process Leading to Pneumonia

Pneumonia-causing agents reach the lungs through different routes:

• In most cases, a person breathes in the infectious organism, which then travels through the airways to the lungs.
• Sometimes, the normally harmless bacteria in the mouth can enter the lungs. This usually happens if the body's "gag reflex," an extreme throat contraction that keeps substances out of the lungs, is not working properly.
• Infections can spread through the bloodstream from other organs to the lungs.

However, in normal situations, the airways protect the lungs from substances that can cause infection.

• The nose filters out large particles.
• If smaller particles pass through, sensors along the airway prompt you to cough or sneeze. This forces many particles back out of the body.
• Tiny particles that reach the small tubes in the lungs (bronchioles) are trapped in a thick, sticky substance called mucus. The mucus and particles are pushed up and out of the lungs by tiny hair-like cells called cilia that beat like a drum. This action is called the "mucociliary escalator."

Click the icon to see an image of respiratory cilia.

• If bacteria or other infectious organisms manage to avoid the airway's defenses, the body's immune system will attack them. Large white blood cells called macrophages destroy the foreign particles.

Click the icon to see an image of a macrophage.

The above-mentioned defense systems normally keep the lung healthy. If these defenses are weakened or damaged, however, bacteria, viruses, fungi, and parasites can easily infect the lung, producing pneumonia.

Click the icon to see an image of the lungs.

Causes

Bacteria are the most common cause of pneumonia. However, pneumonia can also be caused by viruses, fungi, and other agents. It is often impossible to identify the specific culprit.

Many bacteria are grouped into one of two large categories by the laboratory procedure used to look at them under a microscope. The procedure is known as Gram staining. Bacteria are stained with special dyes, then washed in a special solution. The color of the bacteria after washing determines if they are gram-negative or gram-positive bacteria. Knowing which group the bacteria belong to helps your doctor determine how severe the disease is, and how to treat it. Different bacteria are treated with different drugs.

Gram-Positive Bacteria. These bacteria appear blue on the stain and are the most common organisms found in pneumonia. They include:

• Streptococcus pneumoniae (also called S. pneumoniae or the pneumococcus) is the most common cause of pneumonia . This gram-positive bacterium causes about 20 - 60% of all community-acquired bacterial pneumonias (CAPs) in adults. Studies also suggest it causes between 13% to 38% of CAP in children.
• Staphylococcus (S.) aureus, the other major gram-positive bacterium responsible for pneumonia, causes about 2% of CAPs and between 10 - 15% of hospital-acquired pneumonias. It is the organism most often associated with viral influenza, and can develop about five days after the onset of flu symptoms. Pneumonia from S. aureus most often occurs in people with weakened immune systems, very young children, hospitalized patients, and drug abusers who use needles. It is uncommon in healthy adults.
• Streptococcus pyogenes or Group A Streptococcus.

Gram-Negative Bacteria. These bacteria stain pink. Gram-negative bacteria commonly cause infections in hospitalized or nursing home patients, children with cystic fibrosis, and people with chronic lung conditions.

• Haemophilus (H.) influenzae is the second most common organism causing community acquired pneumonia and accounts for 3% to 10% of all cases (generally occurring in patients with chronic lung disease, older patients, and alcoholics).
• Klebsiella pneumoniae may be responsible for pneumonia in alcoholics and in other people who are physically debilitated. It is also associated with recent use of potent antibiotics.
• Pseudomonas aeruginosa is a major cause of pneumonia that occurs in the hospital (hospital-acquired pneumonia). It is a common cause of pneumonia in patients with chronic or severe lung disease.
• Moraxella catarrhalis is found in everyone's nose and mouth. Experts have identified this bacterium as an uncommon cause of certain pneumonias, particularly in people with lung problems, such as asthma or emphysema.
• Neisseria meningitidis is one of the most common causes of meningitis (central nervous system infection), but the organism has been reported in pneumonia, particularly in epidemics of military recruits.
• Other gram-negative bacteria that cause pneumonia include E. coli, Proteus (found in damaged lung tissue), and Enterobacter.

Atypical Pneumonia

Atypical pneumonias produce mild symptoms and a dry cough. Organisms that cause atypical pneumonias include:

• Mycoplasma pneumoniae (M. pneumoniae) is the most common atypical pneumonia organism. Mycoplasma is a very small bacterium that lacks a cell wall. Pneumonia caused by M. pneumoniae spreads when someone carrying the infection is in close contact with others for a long period of time. It is most often found in school-aged children and young adults. The condition, commonly called "walking pneumonia," is usually mild.
• Chlamydia pneumoniae (C. pneumoniae) is now thought to cause 10% of all community-acquired cases of pneumonia. This atypical pneumonia is most common in young adults and children, and it is usually mild. It is less common, but usually more severe, in the elderly.
• Legionella pneumophila causes Legionnaires' disease. You can catch it by breathing in drops of contaminated water. Outbreaks have most often been reported in hotels, cruise ships, and office buildings where people are exposed to contaminated droplets from cooling towers and evaporative condensers. They have also been reported in people who have been near whirlpools and saunas. Legionella pneumophila is not passed on from person to person. Some experts believe the organism causes 29% to 47% of all pneumonia cases.

Legionnaires' disease was first described in 1976 after and outbreak of fatal pneumonia at an American Legion convention. The newly described organism that caused the disease was named Legionella pneumophila, shown in this picture. (Courtesy of the Centers for Disease Control.)

Viral Pneumonia

A number of viruses can cause pneumonia either directly or indirectly. They include:

• Influenza (Flu). Pneumonia is a major serious complication of the flu and can be very serious. It can develop about five days after flu symptoms start. The flu weakens the body's defense systems, making it easier for bacteria to grow in the lungs.
• Respiratory syncytial virus (RSV). Most infants are infected with RSV at some point, but it is most often mild. Still, RSV is a major cause of pneumonia in infants as well as people with damaged immune systems. Studies indicate that RSV pneumonia may be more common in adults than previously thought, especially the elderly.
• Severe acute respiratory syndrome (SARS). SARS is a respiratory infection caused by a newly-described coronavirus, which appears to have jumped from animals to humans. The disease was first reported in China in 2003.
• Human parainfluenza virus. This virus is a leading cause of pneumonia and bronchitis in children, the elderly and in patients with damaged immune systems.
• Adenoviruses. Adenoviruses are common and usually are not problematic, although they have been linked to about 10% of childhood pneumonia.
• Herpesviruses. In adults, herpes simplex virus and varicella-zoster (the cause of chicken pox) can cause pneumonia in people with impaired immune systems.

Aspiration Pneumonia and Anaerobic Bacteria

The mouth contains a mixture of bacteria that is normally harmless. However, if this mixture reaches the lungs, it can cause a serious condition called aspiration pneumonia. This may happen after head injury or general anesthesia, or when a patient takes drugs or alcohol. In such cases, the gag reflex doesn't work as well as it should, so bacteria can enter the airways to the lung. Unlike other organisms that are inhaled, bacteria that cause aspiration pneumonia do not need oxygen to live. These bacteria are called anaerobic bacteria.

Opportunistic Pneumonia

Impaired immunity leaves patients vulnerable to serious, life-threatening pneumonias known as opportunistic pneumonias. They are caused by organisms that are harmless to people with healthy immune systems. Infecting organisms include:

• Pneumocystis carinii, renamed Pneumocystis jiroveci in 2002, is an atypical organism. Originally thought to be protozoa, it is now classified as a fungus. P. jiroveci is very common and generally harmless in people with healthy immune systems. It is the most common cause of pneumonia in AIDS patients.

Click the icon to see an image of pneumocystis carinii.

• Fungi, such as Mycobacterium avium
• Viruses, such as cytomegalovirus (CMV)

Click the icon to see an image of CMV.

In addition to AIDS, other conditions also put patients at risk for opportunistic pneumonia. They include cancers such as lymphoma and leukemia. Long-term use of corticosteroids and drugs known as immunosuppressants also increase a person's risk for these pneumonias.

Occupational and Regional Pneumonias

Exposure to chemicals can also cause inflammation and pneumonia. Where you work and live can put you at higher risk for exposure to pneumonia-causing organisms.

• Workers exposed to cattle, pigs, sheep, and horses are at risk for pneumonia caused by anthrax, Brucella, and Coxiella burnetii, which causes Q fever/

Click the icon to see an image of inhalation anthrax.

• Agricultural and construction workers in the Southwest are at risk for coccidoidomycosis (Valley fever). The disease is caused by the spores of the fungus Coccidioides immitis.
• Those working in Ohio and the Mississippi Valley are at risk for histoplasmosis, a lung disease caused by the fungus Histoplasma capsulatum.

Click the icon to see an image of coccidoidomycosis.

• Workers exposed to pigeons, parrots, parakeets, and turkeys are at risk for psittacosis, a lung disease caused by the bacteria Chlamydia psittaci.
• Hantavirus causes a dangerous form of lung disease. This rare virus is carried by rodents. It does not spread from person to person. Cases have occurred in New Mexico, Arizona, California, Washington, and Mexico.

Click the icon to see an image of the hantavirus.

Symptoms

General Symptoms. The symptoms of bacterial pneumonia develop abruptly and typically include:

• A single episode of shaking chills followed by fever
• Chest pain on the side of lung infection -- severe abdominal pain sometimes occurs in people with pneumonia in the lower lobes of the lung
• Shortness of breath
• Rapid breathing and heart beat
• Cough -- may be dry initially but it eventually produces more fluid (sputum)
• Nausea, vomiting, and muscle aches

Emergency Symptoms. Symptoms of pneumonia indicating a medical emergency include the following:

• High fever
• A rapid heart rate
• Bluish-toned (cyanotic) skin
• Labored and heavy breathing.
• Mental confusion
• Coughing up mucus (sputum) containing pus or blood

Symptoms in the Elderly. It is important to note that older people may have fewer or different symptoms than younger people. Symptoms may come on much more slowly. An elderly person who experiences even a minor cough and weakness for more than a day should seek medical help. Some elderly people may exhibit confusion, lethargy, and general deterioration.

Symptoms of Pneumonia Caused by Anaerobic Bacteria

Pneumonia caused by anaerobic bacteria such as Bacteroides can produce dangerous abscesses in the lungs. People with such pneumonias may have prolonged fever and a productive cough. There is frequently blood in the mucus that is coughed up. Blood may indicate dead lung tissue. About a third of these patients experience weight loss.

Symptoms of Atypical Pneumonia

General Symptoms for Atypical Pneumonias. Atypical pneumonia is most commonly caused by Mycoplasma and usually appears in children and young adults.

The disease progresses gradually.

• General flu-like symptoms often occur first. They may include fatigue, fever, weakness, headache, nasal discharge, sore throat, earache, and stomach and intestinal distress.
• Vague pain under and around the breastbone may occur, but the severe chest pain associated with typical bacterial pneumonia is uncommon.
• Patients may have a severe hacking cough, but it usually does not produce sputum.

Symptoms of Legionnaires' Disease. Symptoms of Legionnaires' disease usually occur more rapidly and include high fever, a dry cough, and shortness of breath. These symptoms are often accompanied by headache, muscle pains, fatigue, gastrointestinal problems, and mental confusion.

Prognosis

More than a million people are hospitalized each year for pneumonia, making it the third most frequent reason for hospitalizations (births are first and heart disease is second). Although the majority of pneumonias respond well to treatment, the infection can still be a very serious problem. It kills between 40,000 and 70,000 people each year.

Outlook for High-Risk Individuals

Hospitalized Patients. For patients who require hospitalization for pneumonia, the death rate is between 10 - 25%. If pneumonia develops in patients already hospitalized for other conditions, the rates are even higher. They range from 50 - 70% and are greater in women than in men.

Older Adults. Community-acquired pneumonia is responsible for 350,000 to 620,000 hospitalizations in the elderly every year. Older adults have lower survival rates than younger people. Even when older individuals recover from community-acquired pneumonia, they have higher than normal death rates over the next several years. Elderly people who live in a nursing home or who are already sick are at particular risk.

Very Young Children. About 20% of deaths in stillborn and very young infants are due to pneumonia. Small children who develop pneumonia and survive are at also at risk for developing lung problems in adulthood.

Pregnant Women. Pneumonia poses a special hazard for pregnant women, possibly due to changes in a pregnant woman's immune system. It is a leading cause of a mother's death.

Patients With Impaired Immune Systems. Pneumonia is particularly serious in people with impaired immune systems. This is particularly true for AIDS patients, in whom pneumonia causes about half of all deaths.

Patients With Serious Medical Conditions. Pneumonia is also very dangerous in people with diabetes, cirrhosis, sickle cell disease, cancer, and in those who have had their spleens removed.

Risk by Organisms

Specific organisms vary in their effects. Mild pneumonia is usually associated with the atypical organisms Mycoplasma and Chlamydia. Severe pneumonia is most often associated with a wide range of organisms. Some are very virulent (potent) but are extremely curable, while others are difficult to treat.

• Mycoplasma and Chlamydia are the most common causes of mild pneumonias and are most likely to occur in children and young adults. They rarely require hospitalization when they are appropriately treated, although recovery may still be prolonged. Severe and life-threatening cases are more likely to occur in elderly people with other medication conditions.
• S. Pneumonia is the most common cause of pneumonia and, in fact, all upper respiratory infections. It can produce severe pneumonia, with mortality rates of 10%. Nevertheless, it is very responsive to many antibiotics.
• Staphylococcus aureus is a gram-positive bacterium that often causes severe pneumonia in hospitalized patients and following influenza A and B in high-risk patients. People who get this form of pneumonia may develop pockets of infection in their lungs (abscesses) that are difficult to treat and can cause death of lung tissue (necrosis). Mortality rates are 30% to 40%, in part because the patients who develop this infection are generally very ill or vulnerable.
• Pseudomonas aeruginosa and Klebsiella pneumonia are gram-negative bacteria that pose a risk for abscesses and severe lung tissue damage.
• Legionella pneumophila is very virulent and can cause widespread damage. Treatments have improved dramatically since it was first identified. However, a 2002 study suggested that many patients experience long-term problems, including coughing, shortness of breath, fatigue and neurological and muscular complications.
• Viral pneumonia is usually very mild, but there are exceptions. Pneumonia associated with influenza can be serious. Respiratory syncytial virus (RSV) pneumonia rarely poses a danger for healthy young adults, but can be life threatening in infants and serious in the elderly. 

Complications of Pneumonia

Abscess. An abscess in the lung is a thick-walled, pus-filled cavity that forms when infection has destroyed lung tissue. It typically occurs as a result of aspiration pneumonia, when a mixture of organisms is carried into the lung. Abscesses can cause hemorrhage (bleeding) in the lung if untreated, but antibiotics that target them have significantly reduced their danger. Abscesses are more common with Staphylococcus aureus or Klebsiella pneumoniae, and uncommon with Streptococcus pneumoniae.

Respiratory Failure. Respiratory failure is one of the top causes of death in patients with pneumococcal pneumonia. Acute respiratory distress syndrome (ARDS) is the specific condition that occurs when the lungs are unable to function and oxygen is so severely reduced that the patient's life is at risk. Failure can occur if pneumonia leads to mechanical changes in the lungs (ventilatory failure) or oxygen loss in the arteries (hypoxemic respiratory failure).

Bacteremia. Bacteremia, bacteria in the blood, is the most common complication of pneumococcus infection, although it rarely spread to others sites. Bacteremia is a frequent complication of infection from other gram-negative organisms, including Haemophilus influenzae.

Pleural Effusions and Empyema. The pleura are two thin membranes that line the chest and lungs:

• The visceral pleura cover the lungs.
• The parietal pleura cover the chest wall.

In some cases of pneumonia, the pleura become inflamed, which can result in breathlessness and acute chest pain when breathing.

In about 20% of pneumonia cases there is build-up of the fluid between the pleural membranes. Ordinarily the narrow zone between the two membranes contains only a tiny amount of fluid, which lubricates the lungs. This build-up of fluid in the pleural space is known as pleural effusion.

In most cases, particularly in Streptococcus pneumoniae, the fluid remains sterile (no bacteria are present), but occasionally it can become infected and even filled with pus, a condition called empyema. Empyema is more likely to occur with specific organisms such as Staphylococcus aureus or Klebsiella pneumoniae infections. The condition can cause permanent scarring.

Collapsed Lung. In some cases, air may fill up the area between the pleural membranes causing the lungs to collapse. This is called pneumothorax. It may be a complication of pneumonia (particularly Streptococcus pneumoniae ) or of the invasive procedures used to treat pleural effusion.

Pneumothorax occurs when air leaks from inside of the lung to the space between the lung and the chest wall. The lung then collapses. The dark side of the chest (right side of the picture) fills with air from outside of the lung tissue.

Other Complications of Pneumonia. In rare cases, infection may spread from the lungs to the heart and possibly throughout the body. This can cause abscesses in the brain and other organs. Severe hemoptysis (coughing up blood) is another potentially serious complication of pneumonia, particularly in patients with other lung problems such as cystic fibrosis.

Long Term Effects of Atypical Pneumonias

The pneumonias cased by the atypical organisms Mycoplasma and Chlamydia are usually mild. Some research suggests, however, that these organisms, particularly Chlamydia, may have powerful inflammatory effects in the blood vessels. This effect may have certain adverse long-term consequences even in healthy younger individuals.

Heart Disease and Stroke. Research has suggested that the C. pneumoniae may trigger the immune system to react, causing inflammation in the coronary arteries. Over time, this can cause hardening of the arteries (atherosclerosis). Atherosclerosis can lead to heart attacks and strokes. Studies on a causal relationship between C. pneumoniae and heart disease have been mixed.

Click the icon to see an image of arterial plaque.

C. pneumoniae has been associated with a thickening in the carotid arteries that lead to the brain -- a risk factor for stroke. It is not clear whether the organism poses any significant risk for stroke.

Click the icon to see an image of atherosclerosis of the internal carotid artery.

Asthma. Chlamydia pneumoniae, Mycoplasma pneumoniae, and RSV are becoming suspects in many cases of severe adult asthma. One small Australian study found evidence of previous C. pneumoniae infection in 64% of the asthmatic patients tested.

Risk Factors

Risk factors for pneumonia often depend on the specific type of disease.

Risk Factors for Community-Acquired Pneumonia (CAP)

CAP is the most common type of pneumonia. It develops outside of the hospital. Each year between two and four million people in the US develop CAP, and 600,000 people are hospitalized. The elderly, infants, and young children are at greatest risk for the disease.

Risk Factors for Hospital-Acquired (Nosocomial) Pneumonia

Pneumonia that is contracted in the hospital is called hospital-acquired or nosocomial pneumonia. It affects an estimated 5  to 10 out of every 1,000 hospitalized patients every year.

Certain individuals, such as the elderly, the very young, and those with chronic or severe medical conditions, are at higher risk.

In addition, the following conditions within the hospital put patients at higher risk:

• Surgery, particularly in people over the age of 80. Among the surgical procedures that pose a particular risk are splenectomy (removal of the spleen), abdominal aortic aneurysm repair, or operations that impair coughing.
• Being in the intensive care unit (ICU). This is particularly true for newborns or patients on breathing machines (mechanical ventilators). In one study, 10% of ICU patients on a breathing machine developed pneumonia. Such patients who lie flat on their backs are at particular risk for aspiration pneumonia. Raising the patient up may reduce this risk.
• Sedation. Hospital patients who receive sedatives also have a higher risk of developing nosocomial pneumonia.

Hospitalized patients are particularly vulnerable to gram-negative bacteria and staphylococci, which can be particularly dangerous in people who are already ill.

Medical Conditions that Pose Risks for Pneumonia

Chronic Lung Disease. Chronic obstructive lung diseases, including chronic bronchitis and emphysema, affect 15 million people in the U.S. This condition is a major risk factor for pneumonia.

Bronchitis is the inflammation of the bronchi, the main air passages to the lungs. It generally follows a viral respiratory infection. Symptoms include coughing, shortness of breath, wheezing, and fatigue.

Click the icon to see an image of emphysema.

People With Compromised Immune Systems. People with impaired immune systems are extremely susceptible to pneumonia. In addition to AIDS, other conditions that compromise the immune system include organ transplantation, chemotherapy, and cancers, especially leukemia and Hodgkin's disease. Patients who are on corticosteroids or other medications that suppress the immune system are also prone to infection.

Gastroesophageal Reflux Disease. Gastroesophageal reflux disease (GERD) is a condition in which acids from the stomach move up into the esophagus. This action is called reflux. Current studies indicate an association between GERD and various problems that occur in the sinuses, ears, nasal passages, and airways of the lung. People with GERD also appear to have an above-average risk for chronic bronchitis, chronic sinusitis, emphysema, pulmonary fibrosis (lung scarring), and recurrent pneumonia. If a person inhales fluid (aspirates) from the esophagus into the lungs, serious pneumonia can occur. GERD may contribute to these conditions by triggering inflammation in these upper passages.

However, GERD drugs may increase one's risk. Patients at high risk for pneumonia should take gastric acid-suppressing drugs only when necessary and at the lowest possible dose.A 2004 study found that the use of gastric acid-suppressing drugs raises the risk of developing community-acquired pneumonia. The highest risks were associated with proton pump inhibitors (PPIs) such as Prilosec and Nexium, but H2-receptor antagonists (e.g., Tagamet, Pepcid) also elevated risk. The researchers theorize that reducing levels of germ-killing stomach acid allow germs to spread in the upper gastrointestinal tract and move into the respiratory tract. The risk posed by these medications is highest in the elderly, children, and patients with asthma, chronic obstructive pulmonary disease, and compromised immune systems.

Click the icon to see an image of gastric reflux.

Factors Associated with a Higher Risk in Healthy Adults

Dormitory or Barrack Conditions. Recruits on military bases and college students living in dormitories are at higher than average risk for Mycoplasma pneumonia. These groups are at lower risk, however, for more serious types of pneumonia.

Smoke and Environmental Pollutants. The risk for pneumonia in people who smoke more than a pack a day is three times that of nonsmokers. Those who are chronically exposed to secondhand cigarette smoke, which can injure airways and damage the cilia, are also at risk. Quitting smoking reduces the risk of dying from pneumonia to normal, but the full benefit takes 10 years to be realized. Toxic fumes, industrial smoke, and other air pollutants may also damage cilia function, which is a defense against bacteria in the lungs.

Drugs and Alcohol. Alcohol or drug abuse is strongly associated with pneumonia. These substances act as sedatives and can diminish the reflexes that trigger coughing and sneezing. Alcohol also interferes with the actions of macrophages, the white blood cells that destroy bacteria and other microbes. Intravenous drug abusers are at risk for pneumonia from infections that originate at the injection site and spread through the blood stream to the lungs.

Specific Risk Factors for Recurrent Pneumonia in Children

Certain children have a higher-than-normal risk for pneumonia and recurrence. Conditions that predispose infants and small children to pneumonia include:

• Impaired immune system
• Gastroesophageal reflux disorder
• Inborn lung or heart defects
• Abnormalities in muscle coordination in the mouth and throat
• Asthma
• Certain genetic disorders such as sickle-cell disease, cystic fibrosis, and Kartagener's syndrome, which results in malfunctioning cilia, the hair-like cells lining the airways

Diagnosis

Diagnostic Difficulties in Community-Acquired Pneumonia (CAP). It is important to determine if the cause of CAP is bacteria, atypical bacteria, or a virus, since they all require different treatments. In children, for example, S. pneumonia is the most common cause, but respiratory syncytial virus may also cause the disease. Although symptoms may differ, they often overlap, which can make it difficult to identify the organism by symptoms alone.

Nevertheless, in many cases of mild-to-moderate community-acquired pneumonia, the physician is able to diagnose and treat pneumonia based solely on a history and physical examination.

Diagnostic Difficulties in Hospital-Acquired (Nosocomial) Pneumonia. Diagnosing pneumonia is particularly difficult in hospitalized patients for a number of reasons:

• Many hospitalized patients have similar symptoms, including fever or signs of lung infiltration on x-rays.
• In hospitalized patients, sputum or blood tests often indicate the presence of bacteria or other organisms, but such agents do not necessarily indicate pneumonia.

Doctors making a diagnosis of pneumonia should rule out other conditions, using a chest x-ray, two sets of blood cultures, a urine analysis for Legionella, and a lung fluid sample, among other tests.

Medical and Personal History

The patient's history is an important part of the diagnosis of pneumonia. The patient should be sure to report any of the following:

• Recent or chronic respiratory infection
• Exposure to people with pneumonia or other respiratory illnesses (such as tuberculosis)
• History of smoking
• Alcohol or drug abuse
• Recent travel
• Occupational risks

Physical Examination

Use of the Stethoscope. The most important diagnostic tool for pneumonia is the stethoscope. Sounds in the chest that may indicate pneumonia are the following:

• Rales (a bubbling or crackling sound). Rales on one side of the chest and rales heard while the patient is lying down are strongly suggestive of pneumonia.
• Rhonchi (abnormal rumblings indicating the presence of thick fluid).
• Percussion. The physician will also use a test called percussion, in which he or she taps the chest lightly. A dull thud, instead of a healthy hollow-drum-like sound, indicates certain conditions that suggest pneumonia. These conditions include including consolidation (a condition in which the lung becomes firm and inelastic), and pleural effusion (fluid build-up in the space between the lungs and the lining around it).

Laboratory Tests for Diagnosing Infection and Identifying Bacterial Agents

Although current antibiotics can destroy a wide spectrum of organisms, it is best to use an antibiotic that targets the specific one making a person sick. Unfortunately, people carry many bacteria, and sputum and blood tests are not always effective in distinguishing between harmless and harmful kinds.

In severe cases, a doctor needs to use invasive diagnostic measures to identify cause of the infection. Standard lab tests used to help diagnose pneumonia include:

Sputum Tests. Looking at the mucus (sputum) sample coughed up from the lungs tells the doctor how sever the disease is. Only a sputum sample will reveal the infecting organism.

The patient coughs as deeply as possible. (A shallow cough produces a sample that usually only contains normal mouth bacteria.) Some patients may need to inhale a saline spray to help them produce an adequate sample. In some cases, a tube will be inserted through the nose down into the lower respiratory tract to induce a deeper cough.

The physician will check the sputum for:

• Blood, which means there is an infection
• Color and consistency -- if it is yellow, green, or brown, infection is likely

A good sputum sample is sent to the laboratory for analysis to look for the presence of bacteria and determine if they are gram-negative or positive.

Blood Tests. The following blood tests may be performed:

• White blood cell count (WBC). High levels indicate infection.
• Blood cultures. Cultures are done to detect the specific organism causing the pneumonia, but they usually can not distinguish between harmless and dangerous organisms. They are accurate in only 10% to 30% of cases. Their use should generally be limited to severe cases.
• Detection of antibodies to S. pneumoniae. Researchers are using specialized techniques to detect antibodies to S. pneumoniae. Antibodies are immune factors that target specific foreign invaders. It is unclear if these techniques are accurate.
• Polymerase Chain Reaction (PCR). In some difficult cases, PCR may be performed. A test makes multiple copies of the genetic material (the RNA) of a virus or bacteria so it becomes detectable.

Urine Tests. A urine test called NOW can detect S. pneumonia within 15 minutes. It may identify up to 77% of pneumonia cases and may rule out the infection in 98% of patients who do not have S. pneumonia. However, it may not be very useful in diagnosing S. pneumoniae as a cause of pneumonia in children.

Laboratory Tests for Less Common Organisms

If uncommon organisms, such as Legionella, Mycoplasma, and Chlamydia organisms, are strongly suspected, more advanced laboratory tests may be used:

• Specialized techniques can detect antibodies to the organisms in blood samples, but these antibodies, such as those responding to Mycoplasma or Chlamydia, are not present early enough in the course of pneumonia to permit prompt diagnosis and treatment.
• PCR is useful for identifying certain atypical strains, including Mycoplasma and Chlamydiapneumoniae and possibly Haemophilus influenzae type b, but it is expensive.
• A urine test can be used to diagnose some cases of Legionnaires' disease.
• Specialized tests called DNA probes are being developed to detect these organisms in respiratory secretions.

Chest X-Rays and Other Imaging Techniques

X-Rays. A chest x-ray is nearly always taken to confirm a diagnosis of pneumonia.

X-rays are a form of electromagnetic radiation (like light). They are of higher energy, however, and can penetrate the body to form an image on film. Structures that are dense (such as bone) will appear white, air will be black, and other structures will be shades of gray depending on density. X-rays can provide information about obstructions, tumors, and other diseases, especially when coupled with the use of barium and air contrast within the bowel.

A chest x-ray may reveal the following:

• White areas in the lung called infiltrates, which indicate infection
• Complications of pneumonia, including pleural effusions and abscesses

Other Imaging Tests. Computed tomography (CT) scans or magnetic resonance imaging (MRI) scans may be useful in some circumstances, especially when:

• X-ray results are unclear
• Patients do not respond to antibiotics
• Complications occur
• Patients have other serious health problems

Click the icon to see an image of a CT scan.

CT and MRI can help detect the presence of tissue damage, abscesses, and enlarged lymph nodes. They can also detect some tumors that block bronchial tubes. No imaging technique can determine the actual organism causing the infection.

Invasive Diagnostic Procedures

Invasive diagnostic procedures may be required when:

• Patients have life-threatening complications
• Standard treatments have failed for no known reason
• AIDS or other immune problems are present

Invasive procedures include:

Thoracentesis. If a doctor detects pleural effusion during the physical exam or on an imaging study, and suspects that empyema (pus) is present, a thoracentesis is performed.

• Fluid in the pleura is withdrawn using a long thin needle inserted between the ribs.
• The fluid is then sent to the lab for multiple tests.

Complications of this procedure are rare, but include collapsed lung, bleeding, and introduction of infection.

Bronchoscopy. A bronchoscopy is done in the following way:

• The patient is given a local anesthetic, supplementary oxygen, and sedatives.
• The physician inserts a fiberoptic tube into the lower respiratory tract through the nose or mouth.
• The tube acts like a telescope into the body, allowing the physician to view the windpipe and major airways and look for pus, abnormal mucus, or other problems.
• The doctor removes specimens for analysis and can also treat the patient by removing any foreign bodies or infected tissue encountered during the process.

Click the icon to see an image of bronchoscopy.

Bronchoalveolar lavage (BAL) may be done at the same time as bronchoscopy. This involves injecting high amounts of saline through the bronchoscope into the lung and then immediately sucking the fluid out. The fluid is then analyzed in the laboratory. Studies find BAL to be an effective method for detecting specific infection-causing organisms.

The procedure is usually very safe, but complications can occur. They include allergic reactions to the sedatives or anesthetics, asthma attacks in susceptible patients, and bleeding. Fever may follow the procedure.

Lung Biopsy. In very severe cases of pneumonia or when the diagnosis is unclear, particularly in patients with damaged immune systems, a lung biopsy may be required. A lung biopsy involves taking some tissue from the lungs and examining it under a microscope.

A Lung Tap. This procedure typically uses a needle inserted between the ribs to draw fluid out of the lung for analysis. It is known by a number of names including lung aspiration, lung puncture, thoracic puncture, transthoracic needle aspiration, percutaneous needle aspiration, and needle aspiration. It is a very old procedure that is not done often any more, particularly in children, since it is invasive and poses a slight risk for collapsed lung. Some experts argue, however, that a lung tap is more accurate than other methods for identifying bacteria and the risk it poses is slight. Given the increase in resistant bacteria, they believe its use should be reconsidered in young people.

Ruling Out Other Disorders that Cause Coughing or Affect the Lung

Common Causes of Persistent Coughing. Over 30 million people seek medical help each year for persistent coughing, which is nearly always temporary and harmless when other symptoms, such as fever, are not present. The four most common causes of persistent coughing are asthma, postnasal drip, gastroesophageal reflux disease (GERD), and chronic bronchitis. Other obvious common causes of chronic cough include heavy smoking or the use of heart drugs known as ACE inhibitors.

Acute Bronchitis. Acute bronchitis is an infection in the passages that carry air from the throat to the lung. The infection causes a cough that produces phlegm. Acute bronchitis is almost always caused by a virus and usually clears up on its own within a few days; in some cases, acute bronchitis caused by a cold can last for several weeks.

Chronic Bronchitis. Chronic bronchitis causes shortness of breath and is often accompanied by infection, mucus production, and coughing, but it is a long-term and irreversible condition. The same microbes that cause pneumonia can cause chronic bronchitis, and symptoms of the two disorders are often similar. They include fatigue, coughing, fever, and production of sputum. There are significant differences between chronic bronchitis and pneumonia:

• Patients with bronchitis are less likely to have wheezing, shortness of breath, chills, very high fevers, and other signs of severe illness.
• Those with pneumonia usually cough up heavy sputum, which is also more likely to contain blood.
• X-rays of patients with bronchitis are unlikely to show fluid or consolidation in the lung.

Asthma. In asthma, the cough is accompanied by wheezing and occurs mostly at night or during activity. Fever is rarely present (unless the patient also has an infection). Asthmatic symptoms from occupational causes can cause persistent coughing, which is usually worse during the work week. Tests called the methacholine inhalation challenge and pulmonary function studies may be effective in diagnosing asthma.

Anthrax. Because of current terrorist concerns, it is important to differentiate between anthrax and community-acquired pneumonia. According to one study, people with inhalation anthrax are more likely to have rapid heart rate and less likely to have headache, nasal symptoms, and muscle aches than those with pneumonia. Laboratory studies with anthrax also show high hematocrit and low albumin and sodium levels. Certain chest x-ray findings also raise the likelihood of anthrax.

Other Disorders that Affect the Lung. Many conditions mimic pneumonia, particularly in hospitalized patients. They include:

• Tuberculosis
• Bronchial asthma
• Bronchiectasis, an irreversible widening of the airways, usually associated with birth defects, chronic sinus or bronchial infection, or blockage
• Atelectasis, a collapse of lung tissue
• Heart failure -- if it affects the left side of the heart, fluid-build up can occur in the lungs and cause persistent cough, shortness of breath, and wheezing.
• Severe allergic reactions, such as reactions to drugs
• Acute respiratory distress syndrome (ARDS)
• Lung cancer
• Interstitial pulmonary fibrosis, a non-infectious inflammation of the lung is marked by progressive damage and scarring

Ruling Out Causes in Children. Important causes of coughing in children at different ages include:

• Asthma
• Physical abnormalities in infants under 18 months
• Sinusitis in children 18 months to 6 years
• Psychologic causes in older children and adolescents

Treatment

Patients with pneumonia are generally treated with:

• Antibiotics
• Respiratory support with oxygen, if needed

Categorizing Severity and Determining the Need for Hospitalization

Up to 10% of all adult hospitalizations in the U.S. are due to pneumonia. Studies indicate that many patients are hospitalized unnecessarily for pneumonia and those patients could be released sooner. A number of strategies are being devised to determine when and which patients can be safely discharged. One approach for determining whether a patient should be hospitalized categorizes patients into five classes depending on risk factors for severity, with class 1 being the least severe (having less than 0.5% risk for death) and class 5 being the most severe (having at least a 10% death risk).

Ruling out the Least Severe Cases. The procedure for determining the need for hospitalization starts by selecting patients in the lowest risk groups (class 1 and 2) who can be discharged with outpatient care only. This can often be done with a simple physical examination, which can rule out a severe condition. Patients in low-risk categories have the following characteristics:

• Under age 50 and not a patient in a nursing home
• No other major illnesses are present
• No serious symptoms are present such as altered mental state, breathing problems, bluish skin, very low blood pressure or very high fever

Even these criteria, however, are flexible. Physicians must use their own judgment and take all factors into consideration. As examples, the following young people with signs of pneumonia should be hospitalized, even if they otherwise fit low-risk (class 1) categories:

• Any infant under a month
• Young adults with alcoholism or severe psychiatric conditions
• Young adults or children with abnormal heart rhythms
• Young adults or children who are vomiting heavily
• Children who are dehydrated

Determining The Next Levels of Severity. If a patient is not in a class 1 category or does not appear to need hospitalization, the next step is to determine which of the other four higher classes the patient fits into. This step involves assigning points to other findings, including:

• Laboratory test results
• X-ray findings
• Demographics (Is the patient male or female? Does the patient live in a nursing home?)

The points are added and the patients are scored:

• Patients who score the lowest are assigned class II and III. They can usually be treated at home or need only to be hospitalized for 24 hours for observation.
• Patients with higher scores are placed in classes IV and V, and are hospitalized.

Home care may be possible even in severe cases when there is good support and available home nursing services. Often, caregivers can even be trained to administer intravenous antibiotics and chest therapy to patients at home.

Home Treatment

Most patients with mild pneumonia can be treated at home with oral antibiotics, typically amoxicillin. A well-conducted 2002 study suggested that children with mild bacterial pneumonia may do as well with three days versus five days of amoxicillin. This is important because shorter duration ensures better compliance.

The following tips are also suggested:

• Patients should be sure to drink plenty of liquids.
• Do not suppress a cough. Coughing is an important reflex for clearing the lungs. Some doctors advise taking expectorants, such as guaifenesin (Breonesin, Glycotuss, Glytuss, Hytuss, Naldecon Senior EX, Robitussin), to loosen mucus. There is no proof that any of these products make much difference in outcome.
• Mild pain can be treated with aspirin (adults only), acetaminophen (Tylenol), or ibuprofen (Advil, Motrin).
• For severe pain, codeine or other stronger pain relievers may be prescribed. It should be noted, however, that codeine and other narcotics suppress coughing, so they should be used with care in pneumonia. Such pain relievers often require monitoring.
• A laboratory study reported that aromatic oils containing oregano, thyme, and rosewood destroyed S. pneumoniae. It is not known whether they have any effect on pneumonia in people, but they are harmless and pleasant in any case.
• Patients should practice chest therapy.

Hospitalization Guidelines

Treatment. If the pneumonia is severe enough for hospitalization, the standard treatment is intravenous administration of antibiotics for five to eight days. In cases of uncomplicated pneumonia, many patients may require only two or three days of intravenous antibiotics followed by oral therapy. Antibiotics taken by mouth are prescribed when the patient has improved substantially or leaves the hospital.

Duration of Stay. In the past, patients remained in the hospital eight to 11 days, but hospital stays are shorter now in most cases. A 2002 study found that patients who were first treated in the emergency room were able to go home sooner than those admitted directly to a hospital room. The reason for this was that ER patients tended to be given the appropriate antibiotics and to be treated sooner than those in the hospital itself.

It is important to stress, in any case, that once patients have been hospitalized, they should remain there until all their vital signs are stable. Most patients become stabilized in three days. Many experts use seven variables to measure such stability and to determine if the patient can go home:

• Temperature. (Opinions differ on temperature goal. Some experts believe that a patient can go home if the temperature levels drop to 101 degrees F. Stricter criteria would require that it be at or close to 98.6 degrees F.)
• Respiration rate. (Goal is a normal breathing rate, although expert opinion differs on the degree of normality required to be discharged.)
• Heart rate. (Goal is 100 beats per minute or less.)
• Blood pressure. (Goal is systolic blood pressure of 90 mmHg or greater.)
• Oxygenation. (Goal of oxygen levels in the blood determined by the physician.)
• The ability to eat. (Goal is regular appetite.)
• Mental function. (Goal is normal.)

Patients or their families should discuss these criteria with the doctor. In a 2002 study, 42% of patients who had two or more signs of instability when they left the hospital were either readmitted or had died within 30 days, compared to 10.5% of completely stabilized patients.

Chest Therapy

Chest therapy using incentive spirometry, rhythmic inhalation and coughing, and chest tapping are all important techniques to loosen the mucus and move it up out of the lungs. It should be used both in the hospital and when the patient returns home during recovery.

Incentive Spirometry. The patient uses an incentive spirometer at regular intervals to improve breathing and loosen sputum. The spirometer is a hand-held clear plastic device that includes a breathing tube and a container with a movable gauge. The patient exhales and then inhales forcefully through the tube, using the pressure of the inhalation to raise the gauge to the highest level possible.

Rhythmic Breathing and Coughing. During recovery, the patient performs rhythmic breathing and coughing every four hours:

• Before starting the breathing exercise, the patient should tap lightly on the chest to loosen mucus within the lung. If available, a caregiver should also tap on the patient's back.
• The patient inhales rhythmically and deeply three or four times.
• The patient then coughs as deeply as possible with the goal of producing sputum.

Medications

Dozens of antibiotics are available that can treat most cases of pneumonia in or out of the hospital, but it is sometimes difficult for the physician to select the best drug. Patients with pneumonia are given a specific antibiotic based on what type of organism is causing the disease. If the organism is unknown, the antibiotic is based on individual risk factors, such as age, health, and severity of the illness.

In determining the appropriate antibiotic, the physician must first answer a number of questions:

• How severe is the pneumonia? Mild-to-moderate cases can be treated at home with oral antibiotics while severe pneumonia usually requires intravenous antibiotics administered in the hospital.
• If the organism causing the pneumonia is not known, was the disorder community- or hospital-acquired? Different organisms are usually involved in each setting, and the physician can often use this information to guess the most likely organism causing the pneumonia.
• If the organism is known, is it typical or atypical? Typical bacterial, community acquired pneumonias for example, are usually caused by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, which have traditionally been treated with penicillin or other standard antibiotics. Such antibiotics, however, do not affect atypical organisms, such as Legionella, Mycoplasma, or Chlamydia. (These organisms are generally treated with a macrolide or possibly a newer quinolone.)
• Does the patient have an impaired immune system, such as in AIDS? Antibiotics used to treat such patients may differ from those used in patients with healthy immune systems.

Once an antibiotic has been chosen, there are still difficulties:

• Individuals respond differently to the same antibiotic depending on age, health, size, and other factors.
• Patients can be allergic to certain antibiotics, thus requiring alternatives.
• Patients may harbor strains of bacteria that are resistant to certain antibiotics.

Antibiotic Treatments for Community-Acquired Pneumonia

For a more detailed discussion of the different types of antibiotics, see the "Antibiotic Classes" section below.

Many cases of community-acquired pneumonia are caused by S. pneumoniae, bacteria that usually respond to antibiotics known as beta lactams (which include penicillin,) and to macrolides. However, resistant strains of S. pneumoniae are increasingly common; most resistant strains respond to newer quinolines or ketolides.

In addition, other important causes of CAP, particularly in younger people, are atypical bacteria, which respond to macrolides (erythromycin, clarithromycin, or azithromycin) or ketolides (telithromycin), or newer quinolones. Such quinolones include levofloxacin (Levaquin), gatifloxacin (Tequin), gemifloxacin (Factive), and moxifloxacin (Avelox).

Antibiotic treatment for CAP is determined by a number of factors including the patient's history of antibiotic therapy, co-existing diseases (COPD, diabetes, heart failure), and where they live(outpatient, hospital patient, nursing home resident). Treatment options can include a single drug, such as levofloxacin or doxycycline, or combination treatment, such as a macrolide administered with a beta-lactam antibiotic.

Antibiotics taken by mouth are generally sufficient for patients whose CAP is mild enough to be treated at home. Intravenous antibiotics are required for hospitalized patients with CAP.

Antibiotic Treatments for Hospital-Acquired (Nosocomial) Pneumonia

Gram-Positive Pneumonia. S. aureus is common in hospital-acquired pneumonia and is a potentially life-threatening infection. Resistance to penicillin is the rule in these cases but certain specialized penicillins such as nafcillin are often still effective. The alternatives to penicillins are first- or second generation cephalosporins. Unfortunately, resistance to these agents is increasing as well. Vancomycin is used for highly resistant bacteria.

Gram-Negative Pneumonia. Patients with hospital-acquired pneumonia are at high risk for infection from gram-negative organisms. Such organisms include Pseudomonas aeruginosa and Klebsiella pneumonia, which require aggressive specific therapy. Powerful antibiotics used against these organisms include the fourth-generation cephalosporins, carbapenems, or ciprofloxacin alone or in combination with an aminoglycides (entamicin or tobramycin). Multidrug therapy may be necessary, particularly for patients, such as those who are on mechanical ventilators, who are at very high risk for multiple dangerous organisms.

Antibiotics for P. Carinii Pneumonia (Common in HIV-Positive Patients)

Trimethoprim-sulfamethoxazole is the antibiotic combination that is the first choice for both preventing and treating P carinii pneumonia in HIV-positive patients. Clindamycin-primaquine may be a good salvage treatment for patients who do not respond to standard therapies.

Side Effects of Antibiotics

Most antibiotics have the following side effects (although specific antibiotics may have other side effects or fewer of the standard ones).

• The most common side effect for nearly all antibiotics is stomach problems.
• Antibiotics raise the risk for vaginal infections. Taking supplements of acidophilus or eating yogurt with active cultures may help restore healthy bacteria that offset the risk for such infections in women.
• Allergic reactions can also occur with all antibiotics but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare but severe, even life-threatening anaphylactic shock.
• Certain drugs, including some over-the-counter medications, interact with antibiotics; patients should inform the physician of all medications they are taking and of any drug allergies.

Surgery

Although most patients with pneumonia do not require invasive therapy, patients with abscess, empyema, or certain other complications may require such treatment.

Surgery (Thoracotomy)

Thoracotomy is the standard surgery for pneumonia. It requires general anesthesia and an incision to open the chest and view the lungs. This procedure allows the surgeon to remove dead or damaged lung tissue. In severe cases, the entire lobe of the lung can be removed. This is called alobectomy. Remaining healthy lung tissue re-expands after surgery to make up for any removed tissue.

Chest Tubes

Chest tubes are used to drain infected pleural fluid. Tubes are not typically required for pneumonia or abscesses. The tubes are inserted after the patient is given a local anesthetic. They remain in place for two to four days, and are removed in one quick movement. It can be very distressing, although some patients experience no discomfort. Complications of chest tubes include infection, accidental injury of the lung, perforation of the diaphragm, and fluid build-up within the lung if the pleural fluid is removed too rapidly. Removing the chest tubes may cause the lung to collapse, requiring the reintroduction of a chest tube to inflate the lung.

Click the icon to see an illustrated series detailing chest tube insertion.

Prevention

The best way to prevent serious respiratory infections such as pneumonia is to avoid those who are sick (if possible), and to practice good hygiene. [For detailed information see the In-Depth Report #94 Colds and influenza.]

Good Hygiene and Preventing Transmission

Colds and flus are spread primarily when an infected person coughs or sneezes near someone else. A very common method for transmitting a cold is by shaking hands. Everyone should always wash his or her hands before eating and after going outside. Ordinary soap is sufficient. Waterless hand cleaners that contain an alcohol-based gel are also effective for every day use and may even kill cold viruses. (They are less effective, however, if extreme hygiene is required. In such cases, alcohol-based rinses are needed.)

Antibacterial soaps add little protection, particularly against viruses. In fact, one study suggests that common liquid dish washing soaps are up to 100 times more effective than antibacterial soaps in killing respiratory syncytial virus (RSV), which is known to cause pneumonia. Wiping surfaces with a solution that contains one part bleach to 10 parts water is very effective in killing viruses.

Dietary Factors

Foods Containing Lactobacilli (Good Bacteria). Friendly bacteria inside the intestines may also help keep you healthy. Researchers are studying the possible protective value of certain strains of lactobacilli bacteria found in the intestines. One such strain is acidophilus, which is used to make yogurt. According to one Finnish study, children attending day care who drank milk containing the strain lactobacilli GG reduced their risk of respiratory infections by 10 - 20%. More research is needed. (The strain used in the Finnish study was not the kind found in most commercial yogurt products.)

Vitamins. Studies are mixed when it comes to whether or not vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place. Two studies in 2002 on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems.

Studies on vitamin E specifically have been largely negative. A 2002 study reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily.

Factors That Lower The Risk for Respiratory Infections

Breastfeeding. Some evidence suggests that women who breastfeed reduce the risk of respiratory infections in their children.

Low Stress and Active Social Life. Several studies have reported that socially active people with low stress have fewer colds than people who have high stress levels or those who have low stress and few social connections.

Zinc

Zinc appears to have certain important effects on the immune system ,and it may have a direct effect on viruses. Zinc preparations in lozenge or nasal gel form are now available as cold treatments. However, research findings regarding zinc's benefits have varied. (The differing results may be due to different zinc preparations.)

• A nasal gel (Zicam), which contains zinc gluconate, has shown some success, possibly because the gel sticks to the nasal passages long enough for the zinc to interact with the virus. In a 2003 study, patients who took the nasal gel within 14 to 48 hours of getting sick had less severe symptoms and felt better faster than those who took a placebo. The finding supports earlier studies reporting that Zicam shortened the duration of a cold by about two days.
• Zinc lozenges are showing mixed results. One 2000 study suggested that the use of zinc acetate lozenges (e.g., Fast-Dry, Galzin) may be more effective and have a better taste than other formulations, such as zinc gluconate (Cold-Eeze, Orazinc). On the other hand, a 2002 study reported that zinc gluconate reduced cold duration significantly. To further confuse matters, the two zinc lozenge preparations were directly compared in a 2000 study, and neither was effective. The reasons for these conflicting results are not clear.
• A small 2001 study on a nasal spray preparation found no benefits. The spray preparation had less zinc than the nasal gel.

In any case, no one with an adequate diet and a healthy immune system should take zinc for prolonged periods for preventing colds.

Side Effects of Zinc. Side effects include:

• Dry mouth.
• Constipation.
• Nausea.
• Bad taste (possibly only with zinc gluconate lozenges).
• Overdose may cause severe vomiting, dehydration, and restlessness. Call a physician if any of these symptoms occur.
• In rare cases, an allergic response may occur.

Food and Drug Interactions. Zinc may also interact with drugs or other elements.

• It may reduce absorption of certain antibiotics.
• Foods high in calcium or phosphorus may reduce zinc absorption.
• In high doses and for long periods of time zinc can cause copper deficiencies.

Anti-Viral Drugs: Neuraminidase Inhibitors

Brands and Benefits. Zanamivir (Relenza) and oseltamivir (Tamiflu) are called neuraminidase inhibitors. They are newer agents that have been designed to block a key viral enzyme called neuraminidase, which helps viruses spread (replicate).

Both zanamivir and oseltamivir have the following benefits:

• Neuraminidase inhibitors are effective for treating both A and B strains of influenza. M2 inhibitors, which prevent the virus from reproducing, are only effective against type A.
• They shorten the duration of the flu by one to three days.
• They may help reduce transmission of the virus, although evidence is needed to confirm these findings.
• They may have a lower risk than M2 inhibitors for emerging viral strains that are resistant to their effects. In fact, on January 14 2006, the Centers for Disease Control and Prevention (CDC) released a Heath Alert (the highest level of importance) regarding the use of M2 inhibitors (amantadine and rimantadine) for the prevention or treatment of flu. Due to significant increase in Influenza A resistance to this class of antiviral medication, the CDC recommended against its use for the remainder of the 2005-2006 flu season.
• They may reduce complications of influenza, although this needs to be confirmed. It is not yet known if they have any effect on overall survival rates.
• They have fewer serious side effects than the M2 inhibitors.
• Both have some benefits for preventing influenza. Only oseltamivir has been approved for this purpose, however, and only in people over 13.

Limitations and Side Effects. Although they have many advantages compared to the M2 inhibitors, they are much more expensive. They also need to be taken within two days of symptoms to be effective. There are also some differences between the two agents that could be significant for some individuals:

• Zanamivir (Relenza) is administered as a nasal spray or inhaler. People with asthma or other lung disorders may experience airway spasms and should use this drug with caution. Side effects are generally minor in most patients. Of concern, however, was a 2001 British study, which found that a majority of elderly patients were not able to properly use the zanamivir (Relenza) inhaler device, making the medicine virtually ineffective in these cases. The study was small, however, and other reports suggest that zanamivir is sill effective in this older group.
• Oseltamivir comes in capsule and liquid form. Side effects are also minor, but about 10 - 15% of patients experience nausea and vomiting. Patients with kidney dysfunction should take lower doses.

Viral Influenza Vaccines (Flu Shot)

Description of Vaccines. Vaccines against the flu (or a "flu shot") use inactivated (not live) viruses. They are designed to provoke the immune system to attack antigens contained on the surface of the virus. Antigens are foreign molecules that the immune system specifically recognizes and targets for attack.

Antigens are large molecules (usually proteins) on the surface of cells, viruses, fungi, bacteria, and some non-living substances such as toxins, chemicals, drugs, and foreign particles. The immune system recognizes antigens and produces antibodies that destroy them.

Unfortunately, the antigens in these influenza viruses undergo genetic alterations (called antigenic drift) over time, so they are likely to become resistant to a vaccine that worked in the previous year. Vaccines are then redesigned annually to match the current strain.

• Influenza A. The influenza A virus is further categorized by primary molecular antigens (hemagglutinin and neuraminidase), which serve as the targets for the vaccines. Influenza A is a particular problem because it can infect other species, such as pigs or chickens, and undergo major genetic changes.
• Influenza B viruses tend to be more stable than influenza A viruses, but they too vary. Although influenza B has been far less common than A, a vaccine for type B is important because experts are concerned that small children will not have developed any immunity to the virus and will experience severe flu if they are exposed to type B.

A live but weakened intranasal vaccine (FluMist) for healthy people aged 5 to 49 years is approved by the FDA. It is known as a live, attenuated, trivalent, intranasal influenza vaccine (LAIV). The vaccine is engineered to grow only in the cooler temperatures of the nasal passages, not in the warmer lungs and lower airways. It boosts the specific immune factors in the mucous membranes of the nose that fight off the actual viral infections. FluMist is a nasal spray. In one study it protected up to 93% of children against the flu.

Timing and Effectiveness of the Vaccine. Ideally, people should get a flu shot every October or November. However, it may take longer for a full supply of the vaccine to reach certain locations. In such cases, the high-risk groups should be served first.

Antibodies to the influenza virus usually develop within two weeks of vaccination. Immunity peaks within four to six weeks, then gradually wears off. That is why most people should get a flu shot every year.

In healthy adults, the flu shot reduces the chance of illness by about 70 - 90%. The current flu vaccines may be slightly less effective in the elderly and those with certain chronic diseases. But, even in people with weak immune systems, the vaccine is usually protective against serious flu complications, particularly pneumonia. In fact, among the elderly, interesting studies are now suggesting that influenza vaccination may help protect against stroke, adverse heart events, and death from all causes.

Children Who Should Be Vaccinated.The American Academy of Pediatrics (AAP) and the CDC recommend flu shots for all healthy children between 6 and 23 months of age. (The flu shot is not approved for children less than 6 months of age.)

In addition, any child over the age of 2 years who has a condition that requires regular medical care or who has been hospitalized for a serious illness (particularly lung or kidney disease, diabetes, sickle cell anemia, or immune deficiencies) should also receive a flu shot. Children who are receiving long-term aspirin therapy should also be immunized against the flu because they are at higher risk for Reye's syndrome, a life-threatening disease, if they get the flu.

Children with Asthma. Recent and major studies have found that the flu shot is safe for children with asthma. It is very important for these patients to reduce their risk for respiratory diseases. Still, 90% of asthma patients remain unvaccinated.

Older Children and Adults Who Should Be Vaccinated. The following, in order of priority, are the population groups who should be vaccinated each year. The first two groups have the highest need for influenza vaccinations and are given top priority:

• All adults 65 years and older. Older adults who receive a flu shot have lower hospitalization rates than those who don't. Evidence now suggests that vaccination may help protect against adverse heart events (including after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two thirds of this group are vaccinated, mostly because of unwarranted fears of ineffectiveness or adverse effects.
• People of any age at high risk for serious complications from influenza. Such people include those with heart disease, lung problems, immune deficiencies, diabetes, kidney disease, or chronic blood disease. (There have been concerns about the safety of the vaccinations in certain high-risk patients such as those with HIV or asthma. Studies now suggest that the vaccine is generally safe in these patient groups. Furthermore, their risk for serious complications from influenza outweighs any potential adverse effects from the vaccines.)
• Adults between the ages of 50 and 64 who have chronic medical conditions. The US Advisory Committee on Immunization Practices (ACIP) suggests that all adults over age 50 should be vaccinated, although this is not recommendation of the CDC.

Other adults who should consider influenza vaccinations include:

• People at risk for flu complications who are traveling to the tropics at any time or to the Southern Hemisphere between April and September.
• Pregnant women who are at risk for flu complications who will be in their second or third trimester during flu season. (Vaccinations should usually be given after the first trimester.)
• Health care providers with direct patient contact, child care providers, and residents of long-term care facilities should also be vaccinated.

Side Effects. Possible side effects include:

• Allergic Reaction. Newer vaccines contain very little egg protein, but an allergic reaction still may occur in people with strong allergies to eggs.
• Soreness at the Injection Site. Up to two thirds of people who receive the influenza vaccine develop redness or soreness at the injection site for one or two days afterward.
• Flu-like Symptoms. Some people actually experience flu-like symptoms, called oculo-respiratory syndrome, which include cough, wheezing, tightness in the chest, and sore throat. Such symptoms tend to occur between 2 and 24 hours after the vaccination and generally last up to two days. These symptoms are not the flu itself, but an immune response to the virus proteins in the vaccine. (Anyone with a fever at the time the vaccination is scheduled, however, should wait to be immunized until the ailment has subsided.)
• Guillain-Barre Syndrome. Isolated cases of Guillain-Barre syndrome occurred in about one of every 100,000 people vaccinated with the swine-flu vaccine in 1976, but it has not been a problem with subsequent vaccines. Guillain-Barre disease can cause paralysis.

Pneumococcal Vaccines

The pneumococcal vaccine protects against S. pneumoniae bacteria, the most common cause of respiratory infections. There are two effective vaccines available: One called a 23-valent polysaccharide vaccine (Pneumovax, Pnu-Immune) for adults, and another called 7-valent conjugate vaccine (Prevnar or PCV7) for infants and young children. Experts are now recommending that more people, including healthy elderly people, be given the pneumococcal vaccine, particularly in light of the increase in antibiotic-resistant bacteria.

Click the icon to see an image of pneumococcal pneumonia.

Pneumococcal Vaccine in Young Children. The pneumococcal vaccine (Prevnar or PCV7) is very effective in children. Evidence suggests that this vaccination, plus the vaccination against Haemophilus influenzae (an important cause of meningitis), has led to 25,000 fewer cases of serious bacterial infections each year.

The pneumococcal vaccine is now recommended by many experts for the following groups:

• All children up to age two. The pneumococcal vaccine (Prevnar or PCV7) has now been added to the Recommended Childhood Immunization Schedule. The pneumococcal vaccine (Prevnar or PCV7) is very effective in children. Studies are suggesting that it prevents common ear infections as well as serious infections, such as pneumonia. In one study, a similar vaccine under investigation protected not only children in day care from serious respiratory infections, but their younger unvaccinated siblings had fewer infections as well.
• Children up to age five who are at risk for pneumonia or complications of influenza, such as children with sickle disease, those with immune deficiencies, or children with chronic medical conditions.
• Other children age two to five who are higher risk for serious pneumococcal infections should be considered for vaccinations. They include African or Native Americans, children in group child care, socially or economically disadvantaged children, or those who have had frequent or complicated acute middle ear infections within the past year. (In one study, the vaccine reduced the number of ear infections episodes by 6%.)

The recommended schedule of immunization for Prevnar (PCV7) is four doses, given at 2, 4, 6, and 12 to 15 months of age. Infants starting immunization between 7 and 11 months should have three doses. Children starting their vaccinations between 12 and 23 months only need two doses. And those who are over two years old need only one dose.

Pneumococcal Vaccine in Older Children and Adults. The vaccine is proving to be help reduce the rate of pneumonia in young adults, although not to the degree that it protects young children. Its benefits for the elderly, other than protection against bloodstream infection, are unclear. Still, pneumonia is declining among adults, which may be due to fewer infections transmitted from vaccinated young children. Many experts now recommend the vaccine for the following older children or adults:

• All people over 65 years old. (Anyone vaccinated more than five years previously should be revaccinated.) The vaccination is protective against pneumococcal bacteremia (blood infection) in this group, but it does not appear to protect against community-acquired pneumonia itself.
• Adults with any chronic condition that increases the risk for pneumonia. This includes patients with heart disease, chronic lung disease (COPD or emphysema, but not asthma), or diabetes.
• Individuals with immune deficiencies, such as HIV, or those undergoing treatments to suppress the immune system.
• Patients with autoimmune diseases, such as rheumatoid arthritis and lupus. Unfortunately, studies suggest the vaccine may not be as effective in these patients as it is in those with healthy immune systems. Nevertheless they are at high risk for serious respiratory infections and should be vaccinated.
• Patients with kidney disease or kidney transplants. Older people who have had transplant operations or those with kidney disease may require a revaccination after six years.
• Patients with problems in the spleen.
• Alcoholics (especially those with cirrhosis).
• People living in long-term care facilities.
• Alaska Natives or American Indians who may be at increased risk for pneumonia.

Because the vaccine is inactive, it is safe for pregnant women and people with immune deficiencies. In fact, when the vaccine is administered to pregnant women, it may actually protect their infants against certain respiratory infections.

Protection lasts for over six years in most people, although it may wear off faster in elderly people than in younger adults. Anyone at risk for serious pneumonia should be revaccinated six years after the first dose, including those who were vaccinated before age 65. Subsequent booster doses, however, are not recommended.

Side Effects. Pain and redness at the injection site, fever, and joint aches are possible with the pneumococcal vaccine. Children are more likely to have fever side effects within 48 hours if they receive other vaccines at the same time. They are also likely to have fewer side effects after the second dose. In rare cases, such local reactions can be severe. Even if a person is mistakenly re-vaccinated before the effects of the first vaccination have worn off, the risk for severe side effects is very low. Allergic reactions are very rare.

Lots More Information

Resources

• www.lungusa.org -- American Lung Association
• www.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
• www.cdc.gov -- Centers for Disease Control and Prevention

References

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Laheij RJ, Sturkenboom MC, Hassing RJ, Dieleman J, Stricker BH, Jansen JB. Risk of community-acquired pneumonia and use of gastric acid–suppressive drugs. JAMA. 2004;292:1955-1960.

Yang ZY, Kong WP, Huang Y, et al. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature. 2004;428(6982):561-564.

Mandell LA, Bartlett JG, Dowell SF, File TM Jr, Musher DM, Whitney C; Infectious Diseases Society of America. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003;37(11):1405-1433.

Apisarnthanarak A, Mundy LM. Etiology of Community-Acquired Pneumonia. Clin Chest Med. 2005;26:47-55.

Stringer JR, Beard CB, Miller RF, Wakefield AE. A new name (Pneumocystis jiroveci) for pneumocystis from humans. Emerg Infect Dis [serial online] 2002;8.

Cohen J, Powderly WG, Berkley SF, et al. eds. Infectious Diseases. 2nd ed. New York, NY: Mosby; 2004:703-706.

Whitty JE, Dombrowski MP. Respiratory Disease in Pregnancy. In: Gabbe SG, Niebyl JR, Simpson JL, et al. eds. Obstetrics: Normal and Problem Pregnancies. 4th ed. New York, NY:  Churchill Livingstone; 2002:1033-36.

US Food and Drug Administration. Product Safety Alerts: Tequin (gatifloxacin). Created: February 15, 2006. Rockville, MD; February 22, 2006.

Centers for Disease Control and Prevention. CDC Health Alert: CDC Recommends against the Use of Amantadine and Rimantadine for the Treatment or Prophylaxis of Influenza in the United States during the 2005-06 Influenza Season. Posted January 14, 2006.