Pulmonary Fibrosis: Causes

Pathogenesis (disease development)

Pulmonary fibrosis is a group of chronic diseases in which there is remodeling of the lung skeleton (increase in connective tissue). In idiopathic pulmonary fibrosis (idiopathic pulmonary fibrosis, idiopathic pulmonary fibrosis IPF), apoptotic alveolar epithelia likely results in the following processes:

  • Disruption of regeneration
  • Activation of fibroblasts (main component of connective tissue).
  • Differentiation into myofibroblasts (cell type first described in wound healing) with increased proliferation.
  • Deposition of extracellular matrix (extracellular matrix, intercellular substance, ECM, ECM).

Etiology (causes)

Biographical causes

Genetic load

  • Mutations in the gene NAF1, which is required for telomere maintenance at the end of chromosomes, can cause hereditary syndromal pulmonary fibrosis.
    • Genetic diseases
      • Hermansky-Pudlak syndrome – genetic disorder with autosomal recessive inheritance associated with albinism, photophobia, and increased bleeding tendency; usually also pulmonary fibrosis and increased bleeding tendency.
      • Niemann-Pick disease (synonyms: Niemann-Pick disease, Niemann-Pick syndrome or sphingomyelin lipidosis) – genetic disease with autosomal recessive inheritance; belongs to the group of sphingolipidoses, which in turn are classified as lysosomal storage diseases; main symptoms of Niemann-Pick disease type A are hepatosplenomegaly (liver and spleen enlargement) and psychomotor decline; in type B, no cerebral symptoms are observed.
      • Neurofibromatosis – genetic disease with autosomal dominant inheritance; belongs to the phakomatoses (diseases of the skin and nervous system); three genetically distinct forms are distinguished:
        • Neurofibromatosis type 1 (von Recklinghausen’s disease) – patients develop multiple neurofibromas (nerve tumors) during puberty, often occurring in the skin but also occurring in the nervous system, orbita (eye socket), gastrointestinal tract (gastrointestinal tract), and retroperitoneum (space located behind the peritoneum on the back toward the spine); The appearance of café-au-lait spots (CALF; light brown macules/spots) and multiple benign (benign) neoplasms is typical
        • [Neurofibromatosis type 2 – characterized by bilateral (bilateral) acoustic neuroma (vestibular schwannoma) and multiple meningiomas (meningeal tumors).
        • Schwannomatosis – hereditary tumor syndrome]
      • Tuberous sclerosis – genetic disease with autosomal dominant inheritance associated with malformations and tumors of the brain, skin lesions and mostly benign tumors in other organ systems.
  • Occupations – bes. Occupations with exposure to asbestos or quartz.

Behavioral causes

  • Consumption of stimulants
    • Tobacco (smoking)
  • Drug use
    • Cocaine
  • Inhalation of noxious agents (tobacco smoke + other noxious agents: see below “Environmental pollution – Intoxications”); but does not occur primarily in smokers; however, former or active smokers have an overall 1.6-fold higher risk

Disease-related causes

  • Allergic alveolitis (hypersensitivity pneumonitis; e.g., farmer’s lung, avian lung).
  • Bronchiolitis obliterans with organizing pneumonia (BOOP): occurs with treatment with amiodarone, gold, and sulfasalazine; may further occur during the course of pneumonia; occurrence in rheumatic and autoimmune diseases (e.g., collagenoses)
  • Chronic interstitial pneumonia (synonyms: interstitial lung disease; pulmonary skeletal disease).
  • Desquamative interstitial pneumonitis (DIP) – interstitial pneumonia occurring primarily in smokers; onset predominantly in the 4th or 4th decade of life.
  • Diabetes mellitus
  • Eosinophilic lung syndrome – heterogeneous group of diseases characterized by accumulation of eosinophilic granulocytes in the alveoli and/or interstitium; causes include allergic bronchopulmonary aspergillosis, autoimmune diseases (e.g., eosinophilic granulomatosis with polyangiitis), helminths, drugs (e.g., cocaine), medications (e.g., phenytoin, L-tryptophan),
  • Usual interstitial pneumonia/pneumonitis (collective term for any form of lung inflammation (pneumonia) that involves the interstitium or intercellular space rather than the alveoli (air sacs)) (UIP).
  • Gastroesophageal reflux disease (synonyms: GERD, gastroesophageal reflux disease; gastroesophageal reflux disease (GERD); gastroesophageal reflux disease (reflux disease); gastroesophageal reflux; reflux esophagitis; reflux disease; Reflux esophagitis; peptic esophagitis) – inflammatory disease of the esophagus (esophagitis) caused by the pathological reflux (reflux) of acid gastric juice and other gastric contents.
  • Pneumonia (pneumonia) – for example, after legionellosis.
  • Rheumatological diseases – dermatomyositis, granulomatosis with polyangiitis, lupus erythematosus, ankylosing spondylitis, polymyositis, rheumatoid arthritis, scleroderma, Sjögren’s syndrome, systemic sclerosis.
  • Sarcoidosis
  • Radiation pneumonitis (radiation pneumonia) – pneumonia resulting from radiation; interstitial lung disease.

Drugs (including drug-induced interstitial lung disease (DILD)).

Environmental pollution – intoxications (poisonings).

  • Herbicides (weed killers) such as paraquat.
  • Inhalation of noxious agents such as tobacco smoke, gases, vapors, aerosols, hairspray, wood dusts, metal dusts (workers in metal smelters), stone dusts (siliceous silica/workers in quarries as well as sandblasters; fibrous silicate minerals: asbestos; beryllium in beryllium processing), as well as plant and animal particles

Other causes

  • Microaspiration of gastric juice
  • Radiatio (radiotherapy) with ionizing radiation.