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.

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.

The primary risk factor for COPD globally is tobacco smoking. Of those who smoke, about 20% will get COPD, and of those who are lifelong smokers, about half will get COPD. In the United States and United Kingdom, of those with COPD, 80–95% are either current smokers or previously smoked. The likelihood of developing COPD increases with the total smoke exposure. Additionally, women are more susceptible to the harmful effects of smoke than men. In nonsmokers, secondhand smoke is the cause of about 20% of cases. Other types of smoke, such as, marijuana, cigar, and water-pipe smoke, also confer a risk. Water-pipe smoke appears to be as harmful as smoking cigarettes. Problems from marijuana smoke may only be with heavy use. Women who smoke during pregnancy may increase the risk of COPD in their child. For the same amount of cigarette smoking, women have a higher risk of COPD than men.

Type 1 respiratory failure is defined as a low level of oxygen in the blood (hypoxemia) without an increased level of carbon dioxide in the blood (hypercapnia), and indeed the PCO may be normal or low. It is typically caused by a ventilation/perfusion (V/Q) mismatch; the volume of air flowing in and out of the lungs is not matched with the flow of blood to the lungs. The basic defect in type 1 respiratory failure is failure of oxygenation characterized by:

This type of respiratory failure is caused by conditions that affect oxygenation such as:

- Low ambient oxygen (e.g. at high altitude)

- Ventilation-perfusion mismatch (parts of the lung receive oxygen but not enough blood to absorb it, e.g. pulmonary embolism)

- Alveolar hypoventilation (decreased minute volume due to reduced respiratory muscle activity, e.g. in acute neuromuscular disease); this form can also cause type 2 respiratory failure if severe

- Diffusion problem (oxygen cannot enter the capillaries due to parenchymal disease, e.g. in pneumonia or ARDS)

- Shunt (oxygenated blood mixes with non-oxygenated blood from the venous system, e.g. right to left shunt)

Hypoxemia (PaO2 6.0kPa).

The basic defect in type 2 respiratory failure is characterized by:

Type 2 respiratory failure is caused by inadequate alveolar ventilation; both oxygen and carbon dioxide are affected. Defined as the buildup of carbon dioxide levels (PCO) that has been generated by the body but cannot be eliminated. The underlying causes include:

- Increased airways resistance (chronic obstructive pulmonary disease, asthma, suffocation)

- Reduced breathing effort (drug effects, brain stem lesion, extreme obesity)

- A decrease in the area of the lung available for gas exchange (such as in chronic bronchitis)

- Neuromuscular problems (Guillain–Barré syndrome, motor neuron disease)

- Deformed (kyphoscoliosis), rigid (ankylosing spondylitis), or flail chest.

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.

Poorly ventilated cooking fires, often fueled by coal or biomass fuels such as wood and dung, lead to indoor air pollution and are one of the most common causes of COPD in developing countries. These fires are a method of cooking and heating for nearly 3 billion people, with their health effects being greater among women due to more exposure. They are used as the main source of energy in 80% of homes in India, China and sub-Saharan Africa.

People who live in large cities have a higher rate of COPD compared to people who live in rural areas. While urban air pollution is a contributing factor in exacerbations, its overall role as a cause of COPD is unclear. Areas with poor outdoor air quality, including that from exhaust gas, generally have higher rates of COPD. The overall effect in relation to smoking, however, is believed to be small.

Acute respiratory distress syndrome (ARDS) has some similarities to IRDS. Transient tachypnea of the newborn presents with respiratory distress syndrome in the preterm newborn.

Giving the mother glucocorticoids speeds the production of surfactant. For very premature deliveries, a glucocorticoid is given without testing the fetal lung maturity. The American College of Obstetricians and Gynecologists (ACOG), Royal College of Medicine, and other major organizations have recommended antenatal glucocorticoid treatment for women at risk for preterm delivery prior to 34 weeks of gestation. Multiple courses of glucocorticoid administration, compared with a single course, does not seem to increase or decrease the risk of death or neurodevelopmental disorders of the child.

In pregnancies of greater than 30 weeks, the fetal lung maturity may be tested by sampling the amount of surfactant in the amniotic fluid by amniocentesis, wherein a needle is inserted through the mother's abdomen and uterus. Several tests are available that correlate with the production of surfactant. These include the lecithin-sphingomyelin ratio ("L/S ratio"), the presence of phosphatidylglycerol (PG), and more recently, the surfactant/albumin (S/A) ratio. For the L/S ratio, if the result is less than 2:1, the fetal lungs may be surfactant deficient. The presence of PG usually indicates fetal lung maturity. For the S/A ratio, the result is given as mg of surfactant per gm of protein. An S/A ratio 55 indicates mature surfactant production(correlates with an L/S ratio of 2.2 or greater).

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.

Congestive heart failure frequently presents with shortness of breath with exertion, orthopnea, and paroxysmal nocturnal dyspnea. It affects between 1–2% of the general United States population and occurs in 10% of those over 65 years old. Risk factors for acute decompensation include high dietary salt intake, medication noncompliance, cardiac ischemia, dysrhythmias, renal failure, pulmonary emboli, hypertension, and infections. Treatment efforts are directed towards decreasing lung congestion.

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

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.

People with chronic obstructive pulmonary disease (COPD), most commonly emphysema or chronic bronchitis, frequently have chronic shortness of breath and a chronic productive cough. An acute exacerbation presents with increased shortness of breath and sputum production. COPD is a risk factor for pneumonia; thus this condition should be ruled out. In an acute exacerbation treatment is with a combination of anticholinergics, beta-adrenoceptor agonists, steroids and possibly positive pressure ventilation.

This refers to a disruption in the ventilation/perfusion equilibrium. Oxygen entering the lungs typically diffuses across the alveolar-capillary membrane into blood. However this equilibration does not occur when the alveolus is insufficiently ventilated, and as a consequence the blood exiting that alveolus is relatively hypoxemic. When such blood is added to blood from well ventilated alveoli, the mix has a lower oxygen partial pressure than the alveolar air, and so the A-a difference develops. Examples of states that can cause a ventilation-perfusion mismatch include:

- Exercise. Whilst modest activity and exercise improves ventilation-perfusion matching, hypoxemia may develop during intense exercise as a result of preexisting lung diseases. During exercise, almost half of the hypoxemia is due to diffusion limitations (again, on average).

- Aging. An increasingly poor match between ventilation and perfusion is seen with age, as well as a decreased ability to compensate for hypoxic states.

- Disease that affect the pulmonary interstitum can also result in hypoxia, by affecting the ability of oxygen to diffuse into arteries. An example of these diseases is pulmonary fibrosis, where even at rest a fifth of the hypoxemia is due to diffusion limitations (on average).

- Diseases that result in acute or chronic respiratory distress can result in hypoxia. These diseases can be acute in onset (such as obstruction by inhaling something or a pulmonary embolus) or chronic (such as chronic obstructive pulmonary disease).

- Cirrhosis can be complicated by refractory hypoxemia due to high rates of blood flow through the lung, resulting in ventilation-perfusion mismatch.

Shunting refers to blood that bypasses the pulmonary circulation, meaning that the blood does not receive oxygen from the alveoli. In general, a shunt may be within the heart or lungs, and cannot be corrected by administering oxygen alone. Shunting may occur in normal states:

- Anatomic shunting, occurring via the bronchial circulation, which provides blood to the tissues of the lung. Shunting also occurs by the smallest cardiac veins, which empty directly into the left ventricle.

- Physiological shunts, occur due to the effect of gravity. The highest concentration of blood in the pulmonary circulation occurs in the bases of the pulmonary tree compared to the highest pressure of gas in the apexes of the lungs. Alveoli may not be ventilated in shallow breathing.

Shunting may also occur in disease states:

- Acute lung injury and adult respiratory distress syndrome, which may cause alveolar collapse. This will increase the amount of physiological shunting, and unlike many forms of shunting, can be managed by administering 100% Oxygen.

- Pathological shunts such as patent ductus arteriosus, patent foramen ovale, and atrial septal defects or ventricular septal defects. These states are when blood from the right side of the heart moves straight to the left side, without first passing through the lungs. This is known as a right-to-left shunt, which is often congenital in origin.

The most common cause is post-surgical atelectasis, characterized by splinting, i.e. restricted breathing after abdominal surgery.

Another common cause is pulmonary tuberculosis. Smokers and the elderly are also at an increased risk. Outside of this context, atelectasis implies some blockage of a bronchiole or bronchus, which can be within the airway (foreign body, mucus plug), from the wall (tumor, usually squamous cell carcinoma) or compressing from the outside (tumor, lymph node, tubercle). Another cause is poor surfactant spreading during inspiration, causing the surface tension to be at its highest which tends to collapse smaller alveoli. Atelectasis may also occur during suction, as along with sputum, air is withdrawn from the lungs. There are several types of atelectasis according to their underlying mechanisms or the distribution of alveolar collapse; resorption, compression, microatelectasis and contraction atelectasis.

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.

The cause of IPF is unknown but certain environmental factors and exposures have been shown to increase the risk of getting IPF. Cigarette smoking is the best recognized and most accepted risk factor for IPF, and increases the risk of IPF by about twofold. Other environmental and occupation exposures such as exposure to metal dust, wood dust, coal dust, silica, stone dust, biologic dusts coming from hay dust or mold spores or other agricultural products, and occupations related to farming/livestock have also been shown to increase the risk for IPF. There is some evidence that viral infections may be associated with idiopathic pulmonary fibrosis and other fibrotic lung diseases.

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

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.

Classically it is cardiogenic (left ventricular) but fluid may also accumulate due to damage to the lung. This damage may be direct injury or injury mediated by high pressures within the pulmonary circulation. When directly or indirectly caused by increased left ventricular pressure pulmonary edema may form when mean pulmonary pressure rises from the normal of 15 mmHg to above 25 mmHg. Broadly, the causes of pulmonary edema can be divided into cardiogenic and non-cardiogenic. By convention cardiogenic refers to left ventricular causes.

Chronic respiratory acidosis may be secondary to many disorders, including COPD. Hypoventilation in COPD involves multiple mechanisms, including decreased responsiveness to hypoxia and hypercapnia, increased ventilation-perfusion mismatch leading to increased dead space ventilation, and decreased diaphragm function secondary to fatigue and hyperinflation.

Chronic respiratory acidosis also may be secondary to obesity hypoventilation syndrome (i.e., Pickwickian syndrome), neuromuscular disorders such as amyotrophic lateral sclerosis, and severe restrictive ventilatory defects as observed in interstitial lung disease and thoracic deformities.

Lung diseases that primarily cause abnormality in alveolar gas exchange usually do not cause hypoventilation but tend to cause stimulation of ventilation and hypocapnia secondary to hypoxia. Hypercapnia only occurs if severe disease or respiratory muscle fatigue occurs.

The atmosphere is composed of 78% nitrogen and 21% oxygen. Since oxygen is exchanged at the alveoli-capillary membrane, nitrogen is a major component for the alveoli's state of inflation. If a large volume of nitrogen in the lungs is replaced with oxygen, the oxygen may subsequently be absorbed into the blood, reducing the volume of the alveoli, resulting in a form of alveolar collapse known as absorption atelectasis.

Central cyanosis is often due to a circulatory or ventilatory problem that leads to poor blood oxygenation in the lungs. It develops when arterial oxygen saturation drops to ≤85% or ≤75%.

Acute cyanosis can be as a result of asphyxiation or choking, and is one of the definite signs that respiration is being blocked.

Central cyanosis may be due to the following causes:

1. Central nervous system (impairing normal ventilation):

- Intracranial hemorrhage

- Drug overdose (e.g. heroin)

- Tonic–clonic seizure (e.g. grand mal seizure)

2. Respiratory system:

- Pneumonia

- Bronchiolitis

- Bronchospasm (e.g. asthma)

- Pulmonary hypertension

- Pulmonary embolism

- Hypoventilation

- Chronic obstructive pulmonary disease, or COPD (emphysema)

3. Cardiovascular diseases:

- Congenital heart disease (e.g. Tetralogy of Fallot, right to left shunts in heart or great vessels)

- Heart failure

- Valvular heart disease

- Myocardial infarction

4. Blood:

- Methemoglobinemia * Note this causes "spurious" cyanosis, in that, since methemoglobin appears blue, the patient can appear cyanosed even in the presence of a normal arterial oxygen level.

- Polycythaemia

- Congenital cyanosis (HbM Boston) arises from a mutation in the α-codon which results in a change of primary sequence, H → Y. Tyrosine stabilises the Fe(III) form (oxyhaemoglobin) creating a permanent T-state of Hb.

5. Others:

- High altitude, cyanosis may develop in ascents to altitudes >2400 m.

- Hypothermia

- Obstructive sleep apnea