We searched PubMed for reports published in English between Jan 1, 1996, and Oct 1, 2016, using the search terms “pulmonary fibrosis”, “fibrosing alveolitis”, “usual interstitial pneumonia”, and “nonspecific interstitial pneumonia”. We mostly selected publications from the past 5 years, although we also included highly regarded older publications. Reviews are cited to provide the reader with additional detail and references.
SeminarIdiopathic pulmonary fibrosis
Section snippets
Epidemiology
Idiopathic pulmonary fibrosis is the most common type of idiopathic interstitial pneumonia. Although the disease has been considered rare, it occurs with similar frequency to that of stomach, brain, and testicular cancers.1, 2 Incidence of idiopathic pulmonary fibrosis has risen over time, and in Europe and North America is estimated to range between 2·8 and 18 cases per 100 000 people per year.2, 3 Little data are available for worldwide variation, but incidence might be lower in Asia and
Pathophysiology
Historically, idiopathic pulmonary fibrosis was considered a chronic inflammatory disorder, which gradually progressed to established fibrosis. However, at the turn of the century, following the recognition that anti-inflammatory therapy did not improve outcome, this concept was reassessed and, subsequently, an immunosuppressive therapeutic strategy incorporating prednisolone and azathioprine was shown to increase mortality.8, 9 Idiopathic pulmonary fibrosis is now generally regarded as a
Clinical presentations, signs, and symptoms
Patients typically present with non-specific symptoms of exertional dyspnoea with or without dry cough (figure 2). This presentation might initially be attributed to ageing, deconditioning, or other comorbidities (eg, smoking history, emphysema, cardiovascular disease, or obesity); therefore, clinical suspicion of idiopathic pulmonary fibrosis by primary care physicians is required to prevent diagnostic delays. Occasionally, patients will present acutely, with days to weeks of respiratory
Diagnosis
Idiopathic pulmonary fibrosis is diagnosed by identification of a pattern of usual interstitial pneumonia on the basis of radiological or histological criteria in patients without evidence of an alternative cause.4, 57, 58 This approach is endorsed in consensus guidelines worldwide and has helped to standardise idiopathic pulmonary fibrosis diagnosis. A major challenge to clinicians is exclusion of other idiopathic interstitial pneumonias and of known causes of interstitial lung disease, such
Clinical management
Prompt referral of patients with known or suspected idiopathic pulmonary fibrosis to a centre with expertise in idiopathic pulmonary fibrosis care is advised, because delayed access is independently associated with increased risk of death.75 Referral provides patients with access to expertise in diagnosis and management, including initiation of disease-modifying therapy, monitoring, side-effect control, and non-pharmacological support (figure 4).4, 76 In addition to idiopathic pulmonary
Disease-modifying therapy
Standardisation of idiopathic pulmonary fibrosis diagnostic criteria has enabled large, multicentre, randomised placebo-controlled trials of proposed disease-modifying drugs. Randomised controlled trials identified that various putative therapies (eg, prednisolone and azathioprine, acetylcysteine, and warfarin) were ineffective or harmful; a landmark contribution to idiopathic pulmonary fibrosis patient care (panel).9, 83 Through these randomised controlled trials, two large phase 3 development
Diagnosis of idiopathic pulmonary fibrosis
Approval of disease-modifying therapies for idiopathic pulmonary fibrosis has increased the focus on early and accurate diagnosis with the aim of improving long-term treatment outcome. The diagnostic certainty of idiopathic pulmonary fibrosis depends on the presence or absence of specific morphological criteria; the approval of safe and effective therapies provides a timely opportunity to review this approach because only patients with idiopathic pulmonary fibrosis can receive these therapies.4
Conclusions and future directions
In less than 10 years, the landscape of idiopathic pulmonary fibrosis has been transformed. Many no longer consider pulmonary fibrosis to be idiopathic, with interaction between causal factors, including genetic polymorphisms, ageing, and environmental exposures, which culminate in a maladaptive repair process of injured lung. Advances in understanding of disease pathogenesis integrated with the establishment of methodologies to do large multicentre randomised controlled trials have resulted in
Search strategy and selection criteria
References (140)
- et al.
Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer
Am J Hum Genet
(2009) - et al.
Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study
Lancet Respir Med
(2013) - et al.
The MUC5B promoter polymorphism is associated with IPF in a Mexican cohort but is rare among Asian ancestries
Chest
(2015) - et al.
Aberrant Wnt/beta-catenin pathway activation in idiopathic pulmonary fibrosis
Am J Pathol
(2003) - et al.
Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium
Am J Pathol
(2004) - et al.
Abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis: the role of ΔN-p63
Lab Invest
(2002) - et al.
Radiologic findings are strongly associated with a pathologic diagnosis of usual interstitial pneumonia
Chest
(2003) - et al.
Obstructive sleep apnea is common in idiopathic pulmonary fibrosis
Chest
(2009) - et al.
Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials
Lancet
(2011) Cancer incidence in five continents
Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review
Eur Resp J
Epidemiology and survival of idiopathic pulmonary fibrosis from national data in Canada
Eur Respir J
An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management
Am J Respir Crit Care Med
Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS)
Am J Respir Crit Care Med
Incidence and prevalence of idiopathic pulmonary fibrosis
Am J Respir Crit Care Med
Clinical course and prediction of survival in idiopathic pulmonary fibrosis
Am J Respir Crit Care Med
Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy
Ann Intern Med
Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis
N Engl J Med
Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis
Am J Respir Crit Care Med
Occupational dust exposure and the aetiology of cryptogenic fibrosing alveolitis
Eur Respir J Suppl
Is idiopathic pulmonary fibrosis an environmental disease?
Proc Am Thorac Soc
Telomerase mutations in families with idiopathic pulmonary fibrosis
N Engl J Med
Adult-onset pulmonary fibrosis caused by mutations in telomerase
Proc Natl Acad Sci USA
A mutation in the surfactant protein C gene associated with familial interstitial lung disease
N Engl J Med
Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening
Nat Genet
Rare variants in RTEL1 are associated with familial interstitial pneumonia
Am J Respir Crit Care Med
Genetic studies provide clues on the pathogenesis of idiopathic pulmonary fibrosis
Dis Model Mech
Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis
Nat Genet
Idiopathic pulmonary fibrosis: a genetic disease that involves mucociliary dysfunction of the peripheral airways
Physiol Rev
A common MUC5B promoter polymorphism and pulmonary fibrosis
N Engl J Med
MUC5B promoter polymorphism and interstitial lung abnormalities
N Engl J Med
Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis
Thorax
A variant in the promoter of MUC5B and idiopathic pulmonary fibrosis
N Engl J Med
Muc5b is required for airway defence
Nature
The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis
Am J Respir Crit Care Med
MUC5B promoter variant rs35705950 affects MUC5B expression in the distal airways in idiopathic pulmonary fibrosis
Am J Respir Crit Care Med
Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis
JAMA
Alveolar progenitor and stem cells in lung development, renewal and cancer
Nature
Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition
Proc Natl Acad Sci USA
Telomere dysfunction in alveolar epithelial cells causes lung remodeling and fibrosis
JCI Insight
Short telomeres are a risk factor for idiopathic pulmonary fibrosis
Proc Natl Acad Sci USA
Extensive phenotyping of individuals at risk for familial interstitial pneumonia reveals clues to the pathogenesis of interstitial lung disease
Am J Respir Crit Care Med
Hyaluronan and TLR4 promote surfactant-protein-C- positive alveolar progenitor cell renewal and prevent severe pulmonary fibrosis in mice
Nat Med
WNT1-inducible signaling protein–1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis
J Clin Invest
Expression of the developmental Sonic hedgehog (Shh) signalling pathway is up-regulated in chronic lung fibrosis and the Shh receptor patched 1 is present in circulating T lymphocytes
J Pathol
Epithelial-mesenchymal interactions in pulmonary fibrosis
Semin Respir Crit Care Med
Role of lung pericytes and resident fibroblasts in the pathogenesis of pulmonary fibrosis
Am J Respir Crit Care Med
Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression
J Cell Biol
Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation
Am J Respir Crit Care Med
Fibrotic extracellular matrix activates a profibrotic positive feedback loop
J Clin Invest
Cited by (1195)
Bletilla striata polysaccharide attenuated the progression of pulmonary fibrosis by inhibiting TGF-β1/Smad signaling pathway
2024, Journal of EthnopharmacologyNiclosamide - encapsulated lipid nanoparticles for the reversal of pulmonary fibrosis
2024, Materials Today Bio