History and exam
Key diagnostic factors
common
presence of risk factors
Key risk factors for IPF include family history, cigarette smoking, advanced age, and male sex.
dyspnoea
Exertional dyspnoea is typically the most prominent and disabling symptom. It is progressive, is not typically episodic (but is reproducible with exertion), and may have been present for >6 months before presentation. See also Assessment of dyspnoea.
cough
Cough is a prominent symptom. It is typically non-productive and can be severe and non-responsive to antitussives.[57] See also Assessment of chronic cough.
crackles
End-inspiratory, bi-basilar crackles are almost universally present on lung examination.[57] These are typically 'dry' and described as 'Velcro' in quality.
Asymptomatic patients may be found on routine clinical lung examination to have bi-basilar inspiratory crackles without signs or symptoms of congestive heart failure. Consequently, these patients may be evaluated first by a cardiologist.
Other diagnostic factors
common
weight loss, fatigue, and malaise
May be present.
uncommon
clubbing
Deformity of the fingers may be present. See also Assessment of clubbing.
Risk factors
strong
advanced age
male sex
A higher proportion of males than females develop idiopathic pulmonary fibrosis.[8]
family history
Prevalence of pulmonary fibrosis is increased 10-fold in families of a patient with a diagnosis of idiopathic pulmonary fibrosis (familial pulmonary fibrosis [FPF]).[16][19]
FPF is mostly indistinguishable from the sporadic form. It typically affects patients at a younger age (mean age at diagnosis is 55-60 years) and follows an autosomal-dominant inheritance pattern in about 80% of cases.[17][18][23]
Incomplete penetrance suggests that the inherited mutation may confer susceptibility to an environmental exposure rather than conferring the disease itself.[20][23][24]
gene mutations and nucleotide polymorphisms
Monogenetic mutations have been discovered in genes implicated in telomere homeostasis (25% to 30%; e.g., TERT, TERC, RTEL1, PARN, DKC1, TINF2, and NAF1), surfactant homeostasis (3% to 5%; e.g., SFTPC, ABCA3, and NFKX2-1), and complex syndromes (3% to 5%; e.g., COPA, TMEM173, HPS-1 to HPS-8, NF1, FAM111B, NDUFAF6, and GATA2).[16][19][20] Most cases (60%) have no known genetic cause.
Genome-wide association studies have revealed common variants associated with IPF among host defence (MUC5B or TOLLIP), cell-cell adhesion (DSP), and DNA repair (TERT or TERC) genes.[19][20] A significant association exists between single-nucleotide polymorphisms (SNPs) in the MUC5B gene, which encodes mucin 5B, and both FPF and idiopathic pulmonary fibrosis (IPF).[25] MUC5B variants (especially rs35705950) are recognised as one of the main risk factors for both IPF development and exacerbations.[20]
cigarette smoking
Tobacco smoke exposure is an independent risk factor for idiopathic pulmonary fibrosis (IPF); risk appears to increase with the intensity of exposure.[26]
Among susceptible people, cigarette smoke likely causes oxidative injury, which in turn triggers the abnormal repair process that is the pathological hallmark of IPF. Genetic predisposition to smoking initiation and lifetime smoking have been associated with a higher risk of IPF.[27]
weak
occupational and environmental exposures
Inhalation of small organic or inorganic particles (including metal dust, wood [pine]) dust), livestock farming, stone cutting/polishing, and raising birds may induce lung injury that can predispose the individual to idiopathic pulmonary fibrosis (IPF).[28]
One meta-analysis found that 44% of patients with IPF report occupational exposure to vapours, gas, dust, and fumes.[29]
gastro-oesophageal reflux
A history of gastro-oesophageal reflux may predispose to the development of idiopathic pulmonary fibrosis, presumably through injury induced by acid aspiration.[30] In the absence of a clear therapeutic effect, guidelines currently recommend against antacid medication and anti-reflux surgery for improving respiratory outcomes.[5]
viral infection
Implicated viruses include hepatitis C, adenovirus, and several herpesviruses (notably cytomegalovirus [CMV] and Epstein-Barr virus [EBV]).[31]
Human herpesviruses (HHV-7, HHV-8, CMV, and EBV) have been identified in 97% of patients with idiopathic pulmonary fibrosis (IPF) compared with only 36% of controls.[32] Persistent or chronic infection with HHV-7, HHV-8, CMV, and EBV (but not HHV-6) significantly increased the risk of developing IPF, but not exacerbations.[33]
Co-infection with viruses and bacteria has been associated with significantly higher mortality and worse respiratory outcomes compared with either infection alone.[34]
bacterial infection
Bacterial infection is a risk factor in the pathogenesis of idiopathic pulmonary fibrosis (IPF).
Less common than viral infection. Pooled bacterial and viral infection prevalences of 54% and 31%, respectively, have been reported in patients with IPF.[35]
Co-infection with viruses and bacteria has been associated with significantly higher mortality and worse respiratory outcomes compared with either infection alone.[34]
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