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.

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.

According to a recent study, the main risk factors for RA-ILD are advancing age, male sex, greater RA disease activity, rheumatoid factor (RF) positivity, and elevated titers of anticitrullinated protein antibodies such as anticyclic citrullinated peptide. Cigarette smoking also appears to increase risk of RA-ILD, especially in patients with human leukocyte antigen DRB1.

A recently published retrospective study by a team from Beijing Chao-Yang Hospital in Beijing, China, supported three of the risk factors listed for RA-ILD and identified an additional risk factor. In that study of 550 RA patients, logistic regression analysis of data collected on the 237 (43%) with ILD revealed that age, smoking, RF positivity, and elevated lactate dehydrogenase closely correlated with ILD.

Recent studies have identified risk factors for disease progression and mortality. A retrospective study of 167 patients with RA-ILD determined that the usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) was a risk factor for progression, as were severe disease upon diagnosis and rate of change in pulmonary function test results in the first 6 months after diagnosis.

A study of 59 RA-ILD patients found no median survival difference between those with the UIP pattern and those without it. But the UIP group had more deaths, hospital admissions, need for supplemental oxygen, and decline in lung function.

PAM is one of the rare lung diseases currently being studied by the Rare Lung Diseases Consortium (RLDC). Pulmonary Alveolar Microlithiasis 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.

ILD may be classified according to the cause. One method of classification is as follows:

1. Inhaled substances

- Inorganic

- Silicosis

- Asbestosis

- Berylliosis

- printing workers (eg. carbon bblack, ink mist)

- Organic

- Hypersensitivity pneumonitis

2. Drug-induced

- Antibiotics

- Chemotherapeutic drugs

- Antiarrhythmic agents

3. Connective tissue and Autoimmune diseases

- Rheumatoid arthritis

- Systemic lupus erythematosus

- Systemic sclerosis

- Polymyositis

- Dermatomyositis

4. Infection

- Atypical pneumonia

- Pneumocystis pneumonia (PCP)

- Tuberculosis

- "Chlamydia" trachomatis

- Respiratory Syncytial Virus

5. Idiopathic

- Sarcoidosis

- Idiopathic pulmonary fibrosis

- Hamman-Rich syndrome

- Antisynthetase syndrome

6. Malignancy

- Lymphangitic carcinomatosis

7. Predominantly in children

- Diffuse developmental disorders

- Growth abnormalities deficient alveolarisation

- Infant conditions of undefined cause

- ILD related to alveolar surfactant region

The disease is more common in males and in tobacco smokers.

In a recent epidemiologic study from Japan, Autoimmune PAP has an incidence and prevalence higher than previously reported and is not strongly linked to smoking, occupational exposure, or other illnesses.

Endogenous lipoid pneumonia and non-specific interstitial pneumonitis has been seen prior to the development of PAP in a child.

PAP 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.

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

Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD), is a group of lung diseases affecting the interstitium (the tissue and space around the air sacs of the lungs). It concerns alveolar epithelium, pulmonary capillary endothelium, basement membrane, perivascular and perilymphatic tissues. It may occur when an injury to the lungs triggers an abnormal healing response. Ordinarily, the body generates just the right amount of tissue to repair damage. But in interstitial lung disease, the repair process goes awry and the tissue around the air sacs (alveoli) becomes scarred and thickened. This makes it more difficult for oxygen to pass into the bloodstream. The term ILD is used to distinguish these diseases from obstructive airways diseases.

In children, several unique forms of ILD exist which are specific for the young age groups. The acronym chILD is used for this group of diseases and is derived from the English name, Children’s Interstitial Lung Diseases – chILD.

Prolonged ILD may result in pulmonary fibrosis, but this is not always the case. Idiopathic pulmonary fibrosis is interstitial lung disease for which no obvious cause can be identified (idiopathic), and is associated with typical findings both radiographic (basal and pleural based fibrosis with honeycombing) and pathologic (temporally and spatially heterogeneous fibrosis, histopathologic honeycombing and fibroblastic foci).

In 2013 interstitial lung disease affected 595,000 people globally. This resulted in 471,000 deaths.

Since the disease was first described in 1918, over 500 case reports have appeared in the literature. PAM is associated with consanguinity. The incidence is higher in Turkey, Japan, India and Italy. The mean age at diagnosis is 35 years based on the cases reported in the literature.

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 exact cause of rheumatoid lung disease is unknown. However, associated factors could be due largely to smoking. Sometimes, the medicines used to treat rheumatoid arthritis, especially methotrexate, may result in lung disease.

Prevention's:

- Stop smoking: Chemicals found in cigarettes can irritate already delicate lung tissue, leading to further complications.

- Having regular checkups: The doctor could listen to lungs and monitor breathing, because lung problems that are detected early can be easier to treat.

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.

Endogenous lipoid pneumonia and non-specific interstitial pneumonitis has been seen prior to the development of pulmonary alveolar proteinosis in a child.

Sources of such lipids could be either exogenous or endogenous.

Exogenous: from outside the body. For example, inhaled nose drops with an oil base, or accidental inhalation of cosmetic oil. Amiodarone is an anti-arrythmic known to cause this condition. Oil pulling has also been shown to be a cause. At risk populations include the elderly, developmentally delayed or persons with gastroesophageal reflux. Switching to water-soluble alternatives may be helpful in some situations.

Endogenous: from the body itself, for example, when an airway is obstructed, it is often the case that distal to the obstruction, lipid-laden macrophages (foamy macrophages) and giant cells fill the lumen of the disconnected airspace.

There is no cure available for asbestosis. Oxygen therapy at home is often necessary to relieve the shortness of breath and correct underlying low blood oxygen levels. Supportive treatment of symptoms includes respiratory physiotherapy to remove secretions from the lungs by postural drainage, chest percussion, and vibration. Nebulized medications may be prescribed in order to loosen secretions or treat underlying chronic obstructive pulmonary disease. Immunization against pneumococcal pneumonia and annual influenza vaccination is administered due to increased sensitivity to the diseases. Those with asbestosis are at increased risk for certain cancers. If the person smokes, quitting the habit reduces further damage. Periodic pulmonary function tests, chest x-rays, and clinical evaluations, including cancer screening/evaluations, are given to detect additional hazards.

Asbestosis is long term inflammation and scarring of the lungs due to asbestos. Symptoms may include shortness of breath, cough, wheezing, and chest pain. Complications may include lung cancer, mesothelioma, and pulmonary heart disease.

Asbestosis is caused by breathing in asbestos fibers. Generally it required a relatively large exposure over a long period of time. Such levels of exposure typically only occur in those who work with the material. All types of asbestos fibers are associated with concerns. It is generally recommended that currently existing asbestos be left undisturbed. Diagnosis is based upon a history of exposure together with medical imaging. It is a type of interstitial pulmonary fibrosis.

There is no specific treatment. Recommendations may include stopping smoking, influenza vaccination, pneumococcal vaccination, or oxygen therapy. Asbestosis affected about 157,000 people and resulted in 3,600 deaths in 2015. Asbestos use has been banned in a number of countries in an effort to prevent disease.

Pulmonary venoocclusive disease is rare, difficult to diagnose, and probably frequently misdiagnosed as idiopathic pulmonary arterial hypertension. Prevalence in parts of Europe is estimated to be 0.1-0.2 cases per million.

PVOD appears to occur as frequently in men as in women, and age at diagnosis ranges from 7–74 years with a median of 39 years. PVOD may occur in patients with associated diseases such as HIV, bone marrow transplantation, and connective tissue diseases. PVOD has also been associated with several chemotherapy regimens such as bleomycin, BCNU, and mitomycin.

Silicosis resulted in 46,000 deaths in 2013 down from 55,000 deaths in 1990.

The genetic cause of pulmonary veno-occlusive disease is mutations in EIF2AK4 gene. Though this does not mean other possible causes do not exist, such as viral infection and risk of toxic chemicals (chemotherapy drugs).

Test articles passing muster in vitro can be evaluated in a number of in vivo models (usually in mice) of ALI including chlorine inhalation, intratracheal instillation of bleomycin and in transforming growth factor β1 (TGF β1) overexpressing transgenic mice exposed to high dose doxycycline. Acute exposure to high concentrations of chlorine gas induces pathological and functional changes in the lungs of rodents. Histological changes consist of epithelial necrosis and detachment, increase in the area of smooth muscle, epithelial regeneration and mucous cell hyperplasia. Most of these abnormalities resolve with time. Functional changes (increased RL and/or bronchial responsiveness to inhaled methacholine) last for mean intervals of 3 and 7 days after exposure, but can persist up to 30 and 90 days, respectively. The functional changes are related to the overall abnormal airway epithelial damage and there is a significant correlation between RL and bronchoalveolar lavage ( BAL) neutrophilia. Bleomycin is an antineoplastic antibiotic drug isolated in 1966 from the actinomycete Streptomyces verticillus. Bleomycin forms a complex with oxygen and metals such as Fe2+, leading to the production of oxygen radicals, DNA breaks, and ultimately cell death. Doxycycline driven overexpression of TGF β1 in the lungs of transgenic mice result in a time-dependent inflammatory response characterized by massive infiltration of F4/80+ monocytic/macrophage-like cells and a wave of apoptotic pulmonary cell death. Mice that survive this initial onslaught go on to demonstrate an increase in lung collagen content, and decreased lung compliance. A large animal model of ALI is the ovine model of body surface burn + heated smoke inhalation. It has been established that combined burn and smoke inhalation injury impairs hypoxic pulmonary vasoconstriction (HPV), the vasoconstrictive response to hypoxia, thereby mismatching ventilation with perfusion. Gas exchange is affected by increases in the dispersion of both alveolar ventilation and cardiac output because bronchial and vascular functions are altered by injury-related factors, such as the effects of inflammatory mediators on airway and vascular smooth muscle tone. As a rule of thumb, all these models are characterized by high mortality, inflammation of the airways and pulmonary parenchyma, edema and flooding of the alveolar spaces by a proteinaceous exudate, sloughing of the airway and pulmonary epithelium, scarring and transition to airway and pulmonary remodeling.

The best way to prevent silicosis is to identify work-place activities that produce respirable crystalline silica dust and then to eliminate or control the dust ("primary prevention"). Water spray is often used where dust emanates. Dust can also be controlled through dry air filtering.

Following observations on industry workers in Lucknow (India), experiments on rats found that jaggery (a traditional sugar) had a preventive action against silicosis.

When comparing the bacterial-caused atypical pneumonias with these caused by real viruses (excluding bacteria that were wrongly considered as viruses), the term "atypical pneumonia" almost always implies a bacterial cause and is contrasted with viral pneumonia.

Known viral causes of atypical pneumonia include respiratory syncytial virus (RSV), influenza A and B, parainfluenza, adenovirus, severe acute respiratory syndrome (SARS)

and measles.

The most common causative organisms are (often intracellular living) bacteria:

- "Chlamydophila pneumoniae": Mild form of pneumonia with relatively mild symptoms.

- "Chlamydophila psittaci": Causes psittacosis.

- "Coxiella burnetii": Causes Q fever.

- "Francisella tularensis": Causes tularemia.

- "Legionella pneumophila": Causes a severe form of pneumonia with a relatively high mortality rate, known as legionellosis or Legionnaires' disease.

- "Mycoplasma pneumoniae": Usually occurs in younger age groups and may be associated with neurological and systemic (e.g. rashes) symptoms.

Atypical pneumonia can also have a fungal, protozoan or viral cause.In the past, most organisms were difficult to culture. However, newer techniques aid in the definitive identification of the pathogen, which may lead to more individualized treatment plans.

A 1998 review noted that life expectancy is usually normal, but that there have occasionally been reported neonatal deaths due to PCD. A 2016 longitudinal study followed 151 adults with PCD for a median of 7 years. Within that span, 7 persons died with a median age of 65.