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.

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

Regardless of cause, UIP is relentlessly progressive, usually leading to respiratory failure and death without a lung transplant. Some patients do well for a prolonged period of time, but then deteriorate rapidly because of a superimposed acute illness (so-called "accelerated UIP"). The outlook for long-term survival is poor. In most studies, the median survival is 3 to 4 years. Patients with UIP in the setting of rheumatoid arthritis have a slightly better prognosis than UIP without a known cause (IPF).

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.

Usual interstitial pneumonia (UIP) is a form of lung disease characterized by progressive scarring of both lungs. The scarring (fibrosis) involves the supporting framework (interstitium) of the lung. UIP is thus classified as a form of interstitial lung disease. The term "usual" refers to the fact that UIP is the most common form of interstitial fibrosis. "Pneumonia" indicates "lung abnormality", which includes fibrosis and inflammation. A term previously used for UIP in the British literature is cryptogenic fibrosing alveolitis, a term that has fallen out of favor since the basic underlying pathology is now thought to be fibrosis, not inflammation.

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.

Alveolar lung disease may be divided into acute or chronic. Causes of acute alveolar lung disease include pulmonary edema (cardiogenic or neurogenic), pneumonia (bacterial or viral), pulmonary embolism, systemic lupus erythematosus, bleeding in the lungs (e.g., Goodpasture syndrome), idiopathic pulmonary hemosiderosis, and granulomatosis with polyangiitis.

Chronic alveolar lung disease can be caused by pulmonary alveolar proteinosis, alveolar cell carcinoma, mineral oil pneumonia, sarcoidosis (alveolar form), lymphoma, tuberculosis, metastases, or desquamative interstitial pneumonia.

Death may occur rapidly with acute, massive pulmonary bleeding or over longer periods as the result of continued pulmonary failure and right heart failure. Historically, patients had an average survival of 2.5 years after diagnosis, but today 86% may survive beyond five years.

Alveolar lung diseases, are a group of diseases that mainly affect the alveoli of the lungs.

Being idiopathic, IPH by definition has an unknown cause. It is thought to be an immune-mediated disease. The lung bleeding causes accumulation of iron, which in itself causes additional lung damage. Meanwhile, there is insufficient iron for inclusion into the haemoglobin molecules inside red blood cells which carry oxygen to body tissues for cellular respiration.

Idiopathic pulmonary haemosiderosis can occur either as a primary lung disorder or as the sequela to other pulmonary, cardiovascular or immune system disorder.

- PH1 involves PH with circulating anti-GBM antibodies.

- PH2 involves PH with immune complex disease such as systemic lupus erythematosus, SLE.

- PH3 involves no demonstrable immune system involvement.

A distinct subset of patients with pulmonary hemosiderosis has hypersensitivity to cow's milk which result in formation of IgG antibodies against basement membrane. This is called Heiner syndrome. Mechanism of haemorrhage is similar as in Goodpasture 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.

Scleroderma in pregnancy is a complex situation; it increases the risk to both mother and child. Overall scleroderma is associated with reduced fetal weight for gestational age. The treatment for scleroderma often includes known teratogens such as cyclophosphamide, methotrexate, mycophenolate, etc. and hence careful avoidance of such drugs during pregnancy is advised. In these cases hydroxychloroquine and low-dose corticosteroids might be used for disease control.

It was identified in 1985, although its symptoms had been noted before but not recognised as a separate lung disease. The risk of BOOP is higher for people with inflammatory diseases like lupus, dermatomyositis, rheumatoid arthritis, and scleroderma.

To date, about 420 cases have been reported in the medical literature. Given its unusual nature, the true prevalence of PB is unknown, and it is likely that many patients are undiagnosed. PB does affect patients of all age groups and both genders.

Pregnancy has been reported to exacerbate LAM in some cases. However, the risk has not been rigorously studied. In a survey of 318 patients who indicated that they had had at least one pregnancy, 163 responded to a second survey focusing on lung collapse. A total of 38 patients reported a pneumothorax with pregnancy, consistent with an incidence of pneumothorax in pregnancy of at least 10% (38 of 318). In one third of patients, the pneumothorax during pregnancy led to the LAM diagnosis. Pneumothoraces were almost twice as frequent on the right as on the left, and four women presented with bilateral spontaneous pneumothorax. Most pneumothoraces took place during the second and third trimesters. This study and others suggest that pregnancy is associated with pleural complications in LAM patients. Few women with a known LAM diagnosis choose to become pregnant and patients in whom LAM is diagnosed during pregnancy rarely have baseline pulmonary function tests available, complicating resolution of this question.

There is no clear obvious cause for scleroderma and systemic sclerosis. Genetic predisposition appears to be limited: genetic concordance is small; still, there is often a familial predisposition for autoimmune disease. Polymorphisms in "COL1A2" and "TGF-β1" may influence severity and development of the disease. There is limited evidence implicating cytomegalovirus (CMV) as the original epitope of the immune reaction, as well as parvovirus B19. Organic solvents and other chemical agents have been linked with scleroderma.

One of the suspected mechanisms behind the autoimmune phenomenon is the existence of microchimerism, i.e. fetal cells circulating in maternal blood, triggering an immune reaction to what is perceived as foreign material.

A distinct form of scleroderma and systemic sclerosis may develop in patients with chronic renal failure. This form, nephrogenic fibrosing dermopathy or nephrogenic systemic fibrosis, has been linked to exposure to gadolinium-containing radiocontrast.

Bleomycin (a chemotherapeutic agent) and possibly taxane chemotherapy may cause scleroderma, and occupational exposure to solvents has been linked with an increased risk of systemic sclerosis.

Bronchiolitis obliterans organizing pneumonia (BOOP), also known as cryptogenic organizing pneumonia, is a form of non-infectious pneumonia; more specifically, BOOP is an inflammation of the bronchioles (bronchiolitis) and surrounding tissue in the lungs. It is often a complication of an existing chronic inflammatory disease such as rheumatoid arthritis, dermatomyositis, or it can be a side effect of certain medications such as amiodarone. BOOP was first described by Gary Epler in 1985.

Some authors have recommended the use of an alternate name, cryptogenic organizing pneumonia (COP), to reduce confusion with bronchiolitis obliterans, a distinct and unrelated disease.

The clinical features and radiological imaging resemble infectious pneumonia. However, diagnosis is suspected after there is no response to multiple antibiotics, and blood and sputum cultures are negative for organisms.

Scleroderma is caused by genetic and environmental factors. Mutations in HLA genes seem to play a crucial role in the pathogenesis of some cases (but not all), likewise silica, aromatic and chlorinated solvents, ketones, trichloroethylene, welding fumes and white spirits exposure seems to contribute to the condition in a small proportion of affected persons.

LAM is almost completely restricted to women. While lung cysts consistent with LAM are reported in some men with tuberous sclerosis, very few of these men develop symptoms. The prevalence of LAM is estimated using data from registries and patient groups and is between 3.4-7.8/million women. The number of new cases each year is between 0.23-0.31/million women/year in the US, UK and Switzerland. The variation between countries and between adjacent states in the US, suggest that a significant number of women with LAM remain either undiagnosed or their symptoms are attributed to other diseases. Adult women with tuberous sclerosis are more likely to develop LAM than women without tuberous sclerosis. Cohorts of patients with tuberous sclerosis have been screened for LAM using CT scanning. In a retrospective study of adults with tuberous sclerosis, CT demonstrated lung cysts in 42% of 95 women and 13% of 91 men. In general, lung cysts were larger and more numerous in women than in men. In a further retrospective study of women with TSC who underwent CT scanning to detect LAM, 25% of those in their 20s had lung cysts whereas 80% of women in their 40s were affected, suggesting that the development of LAM is age dependent at least in tuberous sclerosis-related LAM. Although the prevalence of tuberous sclerosis at 1 in 6000 births is much greater than that of LAM, most pulmonary clinics see more cases of sporadic than tuberous sclerosis-LAM: probably due to a combination of low levels of screening for LAM in tuberous sclerosis and in many, the absence of symptoms.

Female sex and tuberous sclerosis are the only known risk factors. Although use of supplemental estrogen is not associated with development of LAM, one study suggested that use of estrogen-containing contraceptive pills was associated with earlier onset.

It occurs in more than 30% of women with tuberous sclerosis complex (TSC-LAM), a heritable syndrome that is associated with seizures, cognitive impairment and benign tumors in multiple tissues. Most LAM patients who present for medical evaluation have the sporadic form of the disease (S-LAM), however, which is not associated with other manifestations of tuberous sclerosis complex.

Mild cystic changes consistent with LAM have been described in 10–15% of men with TSC, but symptomatic LAM in males is rare. Sporadic LAM occurs exclusively in women, with one published exception to date. Both TSC-LAM and S-LAM are associated with mutations in tuberous sclerosis genes.

Systemic scleroderma, also called diffuse scleroderma or systemic sclerosis, is an autoimmune disease of the connective tissue. It is characterized by thickening of the skin caused by accumulation of collagen, and by injuries to small arteries. There are two forms of scleroderma: localized and systemic. The localized (limited) form affects the skin of only the face, hands, and feet. The systemic (diffuse) form involves those and, in addition, may progress to visceral organs, including the kidneys, heart, lungs, and gastrointestinal tract.

Prognosis is determined by the form of the disease and the extent of visceral involvement. Patients with limited cutaneous scleroderma have a 10-year survival rate of 75%; less than 10% develop pulmonary arterial hypertension after 10 to 20 years. Patients with diffuse cutaneous scleroderma have a 10-year survival rate of 55%. Death is most often caused by lung, heart, and kidney involvement. There is also a slight increase in the risk of cancer.

Survival rates have greatly increased with effective treatment for kidney failure. Therapies include immunosuppressive drugs and, in some cases, glucocorticoids.

The most common organ affected by aspergilloma is the lung. Aspergilloma mainly affects people with underlying cavitary lung disease such as tuberculosis, sarcoidosis, bronchiectasis, cystic fibrosis and systemic immunodeficiency. "Aspergillus fumigatus", the most common causative species, is typically inhaled as small (2 to 3 micron) spores. The fungus settles in a cavity and is able to grow free from interference because critical elements of the immune system are unable to penetrate into the cavity. As the fungus multiplies, it forms a ball, which incorporates dead tissue from the surrounding lung, mucus, and other debris.

CREST syndrome can be noted in up to 10% of patients with primary biliary cirrhosis.

Crest syndrome involves the production of autoimmune anti-nuclear and anti-centromere antibodies, though their cause is not currently understood. There is no known infectious cause.

Shortness of breath is the primary reason 3.5% of people present to the emergency department in the United States. Of these individuals, approximately 51% are admitted to the hospital and 13% are dead within a year. Some studies have suggested that up to 27% of people suffer from dyspnea, while in dying patients 75% will experience it. Acute shortness of breath is the most common reason people requiring palliative care visit an emergency department.

According to the hygiene hypothesis, high levels of cleanliness expose children to fewer antigens than in the past, causing their immune systems to become overactive and more likely to misidentify own tissues as foreign, resulting in autoimmune conditions such as asthma.