The true incidence of TRALI is unknown because of the difficulty in making the diagnosis and because of underreporting. It is estimated to occur in 1:1300 to 1:5000 transfusions of plasma-containing products. TRALI is the leading reported cause of death related to transfusion in the United States; more than 20 cases were reported per year from 2003 to 2005. The immune mediated form of TRALI occurs approximately once every 5000 transfusions and has a mortality of 6–9%.

It is difficult to determine the incidence of TACO, but its incidence is estimated at about one in every 100 transfusions using active surveillance, and in one in every 10000 transfusions using passive surveillance. TACO is the most commonly reported cause of transfusion-related death and major morbidity in the UK, and second most common cause in the USA.

The risk increases with patients over the age of 60, patients with cardiac or pulmonary failure, renal impairment, hypoalbuminemia or anemia.

It is often impossible to distinguish TRALI from adult respiratory distress syndrome. The typical presentation of TRALI is the sudden development of dyspnea, severe hypoxemia (O saturation <90% in room air), hypotension, and fever that develop within 6 hours after transfusion and usually resolve with supportive care within 48 to 96 hours. Although hypotension is considered one of the important signs in diagnosing TRALI, hypertension can occur in some cases.

It may result in death, and it is one of the most common causes of death for people with sickle cell anemia.

VALI is most common in patients receiving mechanical ventilation for acute lung injury or acute respiratory distress syndrome (ALI/ARDS).

Possible reasons for predisposition to VALI include:

- An injured lung may be at risk for further injury

- Cyclic atelectasis is particularly common in an injured lung

Hydroxyurea is a medication that can help to prevent acute chest syndrome. It may cause a low white blood cell count, which can predispose the person to some types of infection.

Transfusion associated circulatory overload is prevented by avoiding unnecessary transfusions, closely monitoring patients receiving transfusions, transfusing smaller volumes of blood at a slower rate, and considering the use of diuretics. A pre-transfusion TACO checklist can be used to assess patients' risk of developing TACO.

24 percent of all patients mechanically ventilated will develop VALI for reasons other than ALI or ARDS. The incidence is probably higher among patients who already have ALI/ARDS, but estimates vary widely. The variable estimates reflect the difficulty in distinguishing VALI from progressive ALI/ARDS.

The annual incidence of ARDS is 13–23 people per 100,000 in the general population. Its incidence in the mechanically ventilated population in intensive care units is much higher. According to Brun-Buisson "et al" (2004), there is a prevalence of acute lung injury (ALI) of 16.1% percent in ventilated patients admitted for more than 4 hours.

Worldwide, severe sepsis is the most common trigger causing ARDS. Other triggers include mechanical ventilation, sepsis, pneumonia, Gilchrist's disease, drowning, circulatory shock, aspiration, traumaespecially pulmonary contusionmajor surgery, massive blood transfusions, smoke inhalation, drug reaction or overdose, fat emboli and reperfusion pulmonary edema after lung transplantation or pulmonary embolectomy. Pneumonia and sepsis are the most common triggers, and pneumonia is present in up to 60% of patients and may be either causes or complications of ARDS. Alcohol excess appears to increase the risk of ARDS. Diabetes was originally thought to decrease the risk of ARDS, but this has shown to be due to an increase in the risk of pulmonary edema. Elevated abdominal pressure of any cause is also probably a risk factor for the development of ARDS, particularly during mechanical ventilation.

The death rate varies from 25–40% in centers using up-to-date ventilatory strategies and up to 58% in all centers.

Clinically, the most serious and immediate complication is acute respiratory distress syndrome (ARDS), which usually occurs within 24 h. Those with significant lower airway involvement may develop bacterial infection. Importantly, victims suffering body surface burn and smoke inhalation are the most susceptible. Thermal injury combined with inhalation injury compromises pulmonary function, producing microvascular hyperpermeability that leads to a significant increase in lung lymph flow and pulmonary edema. The terrorist attack on the World Trade Center on September 11, 2001 left many people with impaired lung function. A study of firefighters and EMS workers enrolled in the FDNY WTC Medical Monitoring and Treatment Program, whose lung function was tested prior to 9/11, documented a steep decline in lung function in the first year after 9/11. A new study that includes a thousand additional workers shows that the declines have persisted over time. Prior to 9/11, 3% of firefighters had below-normal lung function, one year after 9/11 nearly 19% did, and six years later it stabilized at 13%. Ten to 14 days after acute exposure to some agents (e.g. ammonia, nitrogen oxides, sulfur dioxide, mercury), some patients develop bronchiolitis obliterans progressing to ARDS. Bronchiolitis obliterans with organized pneumonia can ensue when granulation tissue accumulates in the terminal airways and alveolar ducts during the body's reparative process. A minority of these patients develop late pulmonary fibrosis. Also at enhanced risk are persons with co-morbidities. Several studies report that both aged persons and smokers are especially vulnerable to the adverse effects of inhalation injury.

IPF has been recognized in several breeds of both dogs and cats, and has been best characterized in West Highland White Terriers. Veterinary patients with the condition share many of the same clinical signs as their human counterparts, including progressive exercise intolerance, increased respiratory rate, and eventual respiratory distress.

Prognosis is generally poor.

The clinical course of IPF can be unpredictable. IPF progression is associated with an estimated median survival time of 2 to 5 years following diagnosis.

The 5-year survival for IPF ranges between 20–40%, a mortality rate higher than that of a number of malignancies, including colon cancer, multiple myeloma and bladder cancer.

Recently a multidimensional index and staging system has been proposed to predict mortality in IPF. The name of the index is GAP and is based on gender [G], age [A], and two lung physiology variables [P] (FVC and DL that are commonly measured in clinical practice to predict mortality in IPF. The highest stage of GAP (stage III) has been found to be associated with a 39% risk of mortality at 1 year. This model has also been evaluated in IPF and other ILDs and shown good performance in predicting mortality in all main ILD subtypes. A modified ILD-GAP Index has been developed for application across ILD subtypes to provide disease-specific survival estimates. In IPF patients, the overall mortality at 5 years rate is high but the annual rate of all-cause mortality in patients with mild to moderate lung impairment is relatively low. This is the reason why change in lung function (FVC) is usually measured in 1-year clinical trials of IPF treatments rather than survival.

In addition to clinical and physiological parameters to predict how rapidly patients with IPF might progress, genetic and molecular features are also associated with IPF mortality. For example, it has been shown that IPF patients who have a specific genotype in the mucin MUC5B gene polymorphism (see above) experience slower decline in FVC and significantly improved survival. Even if such data are interesting from a scientific point of view, the application in the clinical routine of a prognostic model based on specific genotypes is still not possible.

Sixty percent of people with acute interstitial pneumonitis will die in the first six months of illness. The median survival is 1½ months.

However, most people who have one episode do not have a second. People who survive often recover lung function completely.

Since ARDS is an extremely serious condition which requires invasive forms of therapy it is not without risk. Complications to be considered include the following:

- Pulmonary: barotrauma (volutrauma), pulmonary embolism (PE), pulmonary fibrosis, ventilator-associated pneumonia (VAP)

- Gastrointestinal: bleeding (ulcer), dysmotility, pneumoperitoneum, bacterial translocation

- Cardiac: abnormal heart rhythms, myocardial dysfunction

- Kidney: acute kidney failure, positive fluid balance

- Mechanical: vascular injury, pneumothorax (by placing pulmonary artery catheter), tracheal injury/stenosis (result of intubation and/or irritation by endotracheal tube

- Nutritional: malnutrition (catabolic state), electrolyte deficiency.

Medications, substance abuse, and environmental exposures may all trigger eosinophil dysfunction. Medications such as NSAIDs (e.g. ibuprofen), nitrofurantoin, phenytoin, L-tryptophan, daptomycin and ampicillin and drugs of abuse such as inhaled heroin and cocaine may trigger an allergic response which results in EP. Chemicals such as sulfites, aluminum silicate, and cigarette smoke can cause EP when inhaled. A New York City firefighter developed EP after inhalation of dust from the World Trade Center on September 11, 2001.

Pulmonary contusion is found in 30–75% of severe cases of chest injury, making it the most common serious injury to occur in association with thoracic trauma. Of people who have multiple injuries with an injury severity score of over 15, pulmonary contusion occurs in about 17%. It is difficult to determine the death rate (mortality) because pulmonary contusion rarely occurs by itself. Usually, deaths of people with pulmonary contusion result from other injuries, commonly traumatic brain injury. It is controversial whether pulmonary contusion with flail chest is a major factor in mortality on its own or whether it merely contributes to mortality in people with multiple injuries. The estimated mortality rate of pulmonary contusion ranges from 14–40%, depending on the severity of the contusion itself and on associated injuries. When the contusions are small, they do not normally increase the chance of death or poor outcome for people with blunt chest trauma; however, these chances increase with the size of the contusion. One study found that 35% of people with multiple significant injuries including pulmonary contusion die. In another study, 11% of people with pulmonary contusion alone died, while the number rose to 22% in those with additional injuries. Pulmonary contusion is thought to be the direct cause of death in a quarter to a half of people with multiple injuries (polytrauma) who die. An accompanying flail chest increases the morbidity and mortality to more than twice that of pulmonary contusion alone.

Pulmonary contusion is the most common cause of death among vehicle occupants involved in accidents, and it is thought to contribute significantly in about a quarter of deaths resulting from vehicle collisions. As vehicle use has increased, so has the number of auto accidents, and with it the number of chest injuries. However an increase in the number of airbags installed in modern cars may be decreasing the incidence of pulmonary contusion. Use of child restraint systems has brought the approximate incidence of pulmonary contusion in children in vehicle accidents from 22% to 10%.

Differences in the bodies of children and adults lead to different manifestations of pulmonary contusion and associated injuries; for example, children have less body mass, so the same force is more likely to lead to trauma in multiple body systems. Since their chest walls are more flexible, children are more vulnerable to pulmonary contusion than adults are, and thus suffer from the injury more commonly. Pulmonary contusion has been found in 53% of children with chest injuries requiring hospitalization. Children in forceful impacts suffer twice as many pulmonary contusions as adults with similar injury mechanisms, yet have proportionately fewer rib fractures. The rates of certain types of injury mechanisms differ between children and adults; for example, children are more often hit by cars as pedestrians. Some differences in children's physiology might be advantageous (for example they are less likely to have other medical conditions), and thus they have been predicted to have a better outcome. However, despite these differences, children with pulmonary contusion have similar mortality rates to adults.

Eosinophilic pneumonia can develop in several different ways depending on the underlying cause of the disease. Eosinophils play a central role in defending the body against infection by parasites. Many diseases, such as asthma and eczema, are caused when eosinophils overreact to environmental triggers and release an excess of chemicals, e.g. cytokines and histamine. The common characteristic among different causes of EP is eosinophil overreaction or dysfunction in the lung.

Pulmonary contusion can result in respiratory failure—about half of such cases occur within a few hours of the initial trauma. Other severe complications, including infections and acute respiratory distress syndrome (ARDS) occur in up to half of cases. Elderly people and those who have heart, lung, or kidney disease prior to the injury are more likely to stay longer in hospital and have complications from the injury. Complications occur in 55% of people with heart or lung disease and 13% of those without. Of people with pulmonary contusion alone, 17% develop ARDS, while 78% of people with at least two additional injuries develop the condition. A larger contusion is associated with an increased risk. In one study, 82% of people with 20% or more of the lung volume affected developed ARDS, while only 22% of people with less than 20% did so.

Pneumonia, another potential complication, develops in as many as 20% of people with pulmonary contusion. Contused lungs are less able to remove bacteria than uninjured lungs, predisposing them to infection. Intubation and mechanical ventilation further increase the risk of developing pneumonia; the tube is passed through the nose or mouth into the airways, potentially tracking bacteria from the mouth or sinuses into them. Also, intubation prevents coughing, which would clear bacteria-laden secretions from the airways, and secretions pool near the tube's cuff and allow bacteria to grow. The sooner the endotracheal tube is removed, the lower the risk of pneumonia, but if it is removed too early and has to be put back in, the risk of pneumonia rises. People who are at risk for pulmonary aspiration (e.g. those with lowered level of consciousness due to head injuries) are especially likely to get pneumonia. As with ARDS, the chances of developing pneumonia increase with the size of the contusion. Children and adults have been found to have similar rates of complication with pneumonia and ARDS.

Acute interstitial pneumonitis occurs most frequently among people older than forty years old. It affects men and women equally. There are no known risk factors; in particular, smoking is not associated with increased risk.

Given the constant threat of bioterrorist related events, there is an urgent need to develop pulmonary protective and reparative agents that can be used by first responders in a mass casualty setting. Use in such a setting would require administration via a convenient route for e.g. intramuscular via epipens. Other feasible routes of administration could be inhalation and perhaps to a lesser extent oral – swallowing can be difficult in many forms of injury especially if accompanied by secretions or if victim is nauseous. A number of in vitro and in vivo models lend themselves to preclinical evaluation of novel pulmonary therapies.

Fire breathing is typically performed with a high flash point fuel, such as lamp oil (liquid paraffin), while fire eating is performed with low flash point fuels, such as white gas or naphtha. Highly purified fuels are preferred by fire performers due to their minimized toxicity, but other, more dangerous fuels may sometimes be used, such as ethanol, isopropanol, kerosene, gasoline, or charcoal lighter fluid. All fuels run the risk of causing pneumonitis if inhaled, however longer chain oils are more persistent than smaller molecules. Alcohols and volatile naphthas are likely to be absorbed or expelled from the body by evaporation and respiration.

Injury to the lung may also cause pulmonary edema through injury to the vasculature and parenchyma of the lung. The acute lung injury-acute respiratory distress syndrome (ALI-ARDS) covers many of these causes, but they may include:

- Inhalation of hot or toxic gases

- Pulmonary contusion, i.e., high-energy trauma (e.g. vehicle accidents)

- Aspiration, e.g., gastric fluid

- Reexpansion, i.e. post large volume thoracocentesis, resolution of pneumothorax, post decortication, removal of endobronchial obstruction, effectively a form of negative pressure pulmonary oedema.

- Reperfusion injury, i.e. postpulmonary thromboendartectomy or lung transplantation

- Swimming induced pulmonary edema also known as immersion pulmonary edema

- Transfusion Associated Circulatory Overload (TACO) occurs when multiple blood transfusions or blood-products (plasma, platelets, etc.) are transfused over a short period of time.

- Transfusion associated Acute Lung Injury (TRALI) is a specific type of blood-product transfusion injury that occurs when the donors plasma contained antibodies against the donor, such as anti-HLA or anti-neutrophil antibodies.

- Severe infection or inflammation which may be local or systemic. This is the classical form of ALI-ARDS.

Some causes of pulmonary edema are less well characterised and arguably represent specific instances of the broader classifications above.

- Arteriovenous malformation

- Hantavirus pulmonary syndrome

- High altitude pulmonary edema (HAPE)

- Envenomation, such as with the venom of Atrax robustus

Respiratory disease is a common and significant cause of illness and death around the world. In the US, approximately 1 billion "common colds" occur each year. A study found that in 2010, there were approximately 6.8 million emergency department visits for respiratory disorders in the U.S. for patients under the age of 18. In 2012, respiratory conditions were the most frequent reasons for hospital stays among children.

In the UK, approximately 1 in 7 individuals are affected by some form of chronic lung disease, most commonly chronic obstructive pulmonary disease, which includes asthma, chronic bronchitis and emphysema.

Respiratory diseases (including lung cancer) are responsible for over 10% of hospitalizations and over 16% of deaths in Canada.

In 2011, respiratory disease with ventilator support accounted for 93.3% of ICU utilization in the United States.

Pulmonary diseases may also impact newborns, such as pulmonary hyperplasia, pulmonary interstitial emphysema (usually preterm births), and infant respiratory distress syndrome,

Patients, families, and caregivers are encouraged to join the NIH Rare Lung Diseases Consortium Contact Registry. This is a privacy protected site that provides up-to-date information for individuals interested in the latest scientific news, trials, and treatments related to rare lung diseases.