IPF Clinical Features
IPF commonly presents with a chronic dry, nonproductive cough and/or unexplained chronic exertional dyspnea.35810 Chest pain is not a typical manifestation of IPF.
IPF should be considered in all patients with unexplained, chronic exertional dyspnea.358 Dyspnea is one of the prominent and disabling symptoms of idiopathic pulmonary fibrosis. Most patients have experienced dyspnea for more than 6 months before presentation.310 Some patients expect shortness of breath to be part of normal aging, especially during or after physical activity, and may not seek medical attention until much later.11
The cough associated with IPF is often paroxysmal and dry, and can be debilitating.3512
The patient's age at presentation is an important consideration. IPF typically occurs in individuals between 508 and 70 years of age,12 but infrequently in patients younger than 40 years of age.812 IPF is rare in children and therefore other diagnostic possibilities for ILD should be considered in pediatric patients.12 If an older adult develops an interstitial lung disease, IPF is commonly the ultimate diagnosis, with positive predictive value (PPV) based on age alone being 95% for those age 70 or older and close to 100% for those age 75 or older.13 Although no formal recommendations exist, surgical lung biopsy may be deferred in patients over 75 with evidence of a UIP or probable UIP pattern on HRCT and no evidence for connective tissue disease.8
Crackles are detected on auscultation of the lungs in at least 80% of patients with IPF, though these data are not validated in the current diagnostic criteria.3514 Some experts believe that crackles are essentially universal in the diagnosis of IPF.15 If crackles are absent, other forms of lung disease (eg, granulomatous disease) should be considered.16
The crackles of IPF are pan- or end-inspiratory, have a “Velcro-like” character, and are heard predominantly in lower posterior lung zones.1217 With disease progression, crackles may extend toward the mid- and upper-lung zones.15 To learn more about the respiratory sounds associated with IPF and how they differ from normal lung sounds and sounds associated with COPD, see Resource Center.
Digital clubbing is present in up to 50% of patients with IPF (Figure 1).35814
Other physical manifestations of IPF are rare, but may include cyanosis, and/or signs of pulmonary hypertension or right heart failure.1018
Constitutional symptoms are rare.10 Notably, fever, weight loss, and arthritis are unusual in IPF and should prompt investigation for secondary causes of pulmonary fibrosis such as connective tissue disease.12 By definition, patients with pulmonary fibrosis and a connective tissue disease diagnosis do not have IPF.8
In all cases of potential ILD, a detailed medical history is essential, focusing on social history, occupational and environmental exposures, drug exposures, family history, comorbidities, and a comprehensive review of systems.8
Cigarette smoking is strongly associated with IPF, especially among patients with a history of smoking more than 20-pack-years.19 Many patients are former smokers at the time of IPF diagnosis.319 For more information about smoking as a potential risk factor for IPF, see Natural History and Potential Risk Factors.
Case-controlled studies have examined the association between various environmental or occupational exposures and the risk of developing IPF.20 Several of these studies observed an increased risk of developing IPF among patients with exposure to certain environmental factors, including metal dust exposure, wood dust exposure, sand, stone, and silica exposure, as well as agriculture/farming-related and livestock-related exposures.
While such exposures are associated with IPF, they have not been found to be causative. In contrast, hypersensitivity pneumonitis (HP), a granulomatous inflammatory lung disorder, is typically caused by inflammatory reaction to inhaled organic particles.21 Common exposures associated with HP are specific fungi, bird feathers (such as in household bedding), and atypical mycobacterium (such as those that colonize hot tubs),21 though a myriad of causes have been described. Potential etiologic agents of HP are shown in Table 1.22
|Fungal and Bacterial|
|Farmer's lung||Moldy hay, grain, silage|
|Ventilation pneumonitis; humidifier lung; air conditioner lung||Contaminated forced-air systems; water reservoirs|
|Bagassosis||Moldy sugarcane (ie, bagasse)|
|Mushroom worker's lung||Moldy mushroom compost|
|Enoki mushroom worker's lung (Japan)||Moldy mushroom compost|
|Detergent lung; washing powder lung||Detergents (during processing or use)|
|Malt worker's lung||Moldy barley|
|Sequoiosis||Moldy wood dust|
|Maple bark stripper's lung||Moldy maple bark|
|Cheese washer's lung||Moldy cheese|
|Woodworker's lung||Oak, cedar, and mahogany dust, pine and spruce pulp|
|Hardwood worker's lung||Kiln-dried wood|
|Paprika slicer's lung||Moldy paprika pods|
|Sauna taker's lung||Contaminated sauna water|
|Familial HP||Contaminated wood dust in walls|
|Wood trimmer's lung||Contaminated wood trimmings|
|Basement shower HP||Mold on unventilated shower|
|Hot tub lung||Hot tub mists; mold on ceiling|
|Wine maker's lung||Mold on grapes|
|Woodsman's disease||Oak and maple trees|
|Thatched roof lung||Dead grasses and leaves|
|Tobacco grower's lung||Tobacco plants|
|Potato riddler's lung||Moldy hay around potatoes|
|Summer-type pneumonitis||Contaminated old houses|
|Dry rot lung||Rotten wood|
|Machine operator's lung||Aerosolized metalworking fluid|
|Residential provoked pneumonitis Amebae||Residential exposure|
|Humidifier lung||Contaminated water from home humidifier, ultrasonic misting fountains|
|Shower curtain disease||Moldy shower curtain|
|Pigeon breeder's or pigeon fancier's disease||Parakeets, budgerigars, pigeons, chickens, turkeys|
|Pituitary snuff taker's lung||Bovine and porcine pituitary proteins|
|Fish meal worker's lung||Fish meal dust|
|Bat lung||Bat droppings|
|Furrier's lung||Animal pelts|
|Animal handler's lung; laboratory worker's lung||Urine, serum, pelts, proteins|
|Miller's lung||Dust-contaminated grain|
HP = hypersensitivity pneumonitis
Differentiation between IPF and HP can be difficult, but is essential, as the workup and treatment are vastly different.23 In HP, allergen avoidance is mandatory and can be curative, which differs from IPF. Systemic corticosteroids are recommended for treatment in HP21 but are strongly discouraged as IPF treatment.8 If HP is suspected by history, serologic workup including fungal antigen panels and immunoglobulin G levels toward the suspected offending antigen are suggested.21
For more information about environmental exposures, see Natural History and Potential Risk Factors.
Numerous drugs have been associated with development of ILD.24 Drugs commonly associated with the development of ILD include bleomycin and other chemotherapeutic agents, nitrofurantoin, amiodarone, and methotrexate.25 The website Pneumotox (www.pneumotox.com) is freely available and accessible as an aid in the diagnostic process of potential drug-induced ILD and can be indexed by drug name or pathologic pattern.
Patients with suspected IPF should be carefully evaluated for other known causes of ILD (domestic and occupational environmental exposures, connective tissue disease, and drug toxicity).8
Genetic factors have been investigated in both familial and sporadic cases of IPF.8 Familial and sporadic IPF, may be clinically and/or histologically indistinguishable, with familial forms being suspected based on family history or in patients younger than 50 years of age.8 While routine genetic testing cannot be recommended at this time in patients with sporadic IPF8 the rapid accumulation of genetic information and the changes in understanding of their functional consequences makes this a rapidly changing field. For more information on the genetic abnormalities associated with IPF, see Pathogenesis.
Gastroesophageal reflux disease (GERD) is strongly associated with IPF, although a cause-and-effect relationship has not been established.8 The estimated prevalence may be as high as 90% in patients with IPF but may be present without symptoms.26 For more information about GERD as a potential risk factor for IPF, see Natural History and Potential Risk Factors.
Because IPF occurs in older individuals, it is not uncommon for comorbid conditions (such as emphysema, coronary artery disease, congestive heart failure, or obstructive sleep apnea) to also be present.827 Pulmonary hypertension, either due to chronic hypoxia28 or as a result of interstitial lung disease29 may also be present.
The incidence of lung cancer is seven times higher in IPF patients compared to patients without IPF; this finding persists even when controlling for smoking history.30
Rheumatologic Review of Symptoms
Patients with suspected IPF should be carefully evaluated for signs and symptoms suggestive of a potential connective tissue disease, such as arthralgias, synovitis, joint effusions, morning joint stiffness, proximal muscle weakness, fever, photosensitivity, Raynaud's phenomenon, pleuritis, or sicca symptoms (ie, dry eyes).31 Patients with ILD and clinical signs or symptoms that meet the diagnostic criteria for connective tissue disease do not have IPF.8
No specific laboratory abnormalities are associated with, or diagnostic for, IPF.12
Serologic testing should be performed in the evaluation of patients with suspected IPF to exclude occult connective tissue disease.8 The ATS/ERS/JRS/ALAT 2011 guidelines recommend evaluating rheumatoid factor, anti-cyclic citrullinated peptide (CCP), and anti-nuclear antibody (ANA) titer and pattern, even if the patient has no symptoms that would suggest connective tissue disease.8
Antisynthetase antibodies, creatine kinase and aldolase, Sjögren's antibodies, and scleroderma antibodies should be evaluated based on symptoms (Table 2).832
|Signs and Symptoms||Laboratory Test||Disease|
|All patients with suspected IPF|
|Dry mouth (Sicca syndrome)
|Proximal muscle pain or weakness
Low-level titers of ANA (less than 1:160) or rheumatoid factor occur in 10% to 20% of patients with IPF.7 Such patients should be screened for signs and symptoms of connective tissue disease (eg, arthritis, Raynaud's phenomenon, skin changes, abnormal esophageal motility).8 If there is no additional serologic and/or clinical evidence to support a connective tissue diagnosis, a diagnosis of IPF is appropriate.8 A high titer of autoantibodies suggests an alternative diagnosis.12
Notably, in up to 10% of patients with signs or symptoms suggestive of connective tissue disease, initial serologic testing may be non-revealing.33 If a strong clinical suspicion of connective tissue disease exists, repeating a serologic panel 6 to 12 months after initial testing may be warranted.834 At each clinical encounter, a re-evaluation of targeted symptoms and physical exam should be performed to ensure no new rheumatologic findings have emerged.8
An electrocardiogram in patients with suspected IPF may reveal pulmonary vascular abnormalities.35 Patients with pulmonary hypertension may demonstrate right ventricular hypertrophy or right bundle branch block patterns.35 Those with concurrent cardiac disease may have abnormalities on electrocardiogram which may be present prior to the development of respiratory symptoms.
Patients with suspected IPF should undergo full pulmonary function testing, which includes spirometry, complete lung volume assessment, and evaluation of diffusing capacity for carbon monoxide.1
Measurement of lung volumes typically shows a reduction in total lung capacity (TLC) in patients with IPF, confirming restrictive physiology.712 Decreased TLC is due to accumulation of parenchymal scar tissue, loss of intrinsic elasticity, and subsequent distortion of normal lung architecture.12
Routine spirometry without full lung volumes may be appropriate in the initial evaluation of patients with unexplained exertional dyspnea. In patients with IPF, spirometry typically shows the following:
- Decreased measures of forced vital capacity (FVC) and forced expiratory volume (FEV) in 1 second (FEV1)12
- Increased ratio of FEV1/FVC, consistent with restrictive physiology12
Measurement of diffusion capacity of the lungs (DL) often reveals impaired gas exchange in patients with IPF.12 The reduction in DL can occur prior to a reduction in lung volume and can be found during the early stages of IPF.12
In patients with concomitant IPF and COPD, spirometric measures (FEV1, FVC, and FEV1/FVC) and lung volumes (TLC) may be normal; however, DL will invariably be low.3637 Abnormal pulmonary function tests need not be present when establishing a diagnosis of IPF.2
The resting arterial blood gas may be normal or abnormal in patients with IPF. Oftentimes relative or absolute hypoxia precedes hypercapnia in those with IPF.12 While the oxygen saturation may be normal at rest, oxygen desaturation is commonly observed during exercise.12
For more information about FVC and other measures of pulmonary function see Clinical Assessments.
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Content contributed by:
Ryan Hadley, MD
University of Michigan