Clinical Features of IPF

COMMON SIGNS OF IPF^1,5-8

• Dyspnea
• Dry, nonproductive cough
• Crackles on auscultation
• Digital clubbing

RARE SIGNS OF IPF^9,10

• Cyanosis
• Signs of right heart failure

Constitutional signs and connective tissue disorders (CTDs) are rare in IPF:^3,9

• Fever
• Weight loss
• Arthritis or other CTDs

These signs should prompt investigation into secondary causes of pulmonary fibrosis.³

DYSPNEA

Dyspnea is nearly universal in IPF.⁸ It’s one of the prominent and disabling symptoms of IPF.⁸

Most patients have experienced dyspnea for more than 6 months before presentation.^5,8 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

IPF should be considered in all patients with unexplained, gradual onset of chronic dyspnea (either exertional or at rest).^5,8

COUGH

Cough is a nearly universal symptom of IPF.

• Most — if not all — patients with IPF have a chronic, dry/nonproductive coughs^8,12
• Wheezing is not common in IPF and suggests airway disease rather than interstitial disease¹³
• Chronic cough significantly impairs patients’ quality of life (QOL)¹⁴
• Persistent and excessive cough may cause serious complications, including:¹⁵
  • Cough-related syncope
  • Pneumothorax
  • Cardiac arrhythmias
  • Seizures

CRACKLES

At least 80% of patients with IPF have crackles on auscultation.^5-7

• The crackles of IPF are pan- or end-inspiratory, and are heard predominantly in lower posterior lung zone^3,16
• With disease progression, crackles may extend toward the mid- and upper-lung zones¹⁷

Some experts believe that crackles are essentially universal in the diagnosis of IPF.¹⁷ However, the correlation of crackles and IPF has not been validated in the current diagnostic criteria.^1,17 If crackles are absent, other forms of lung disease (e.g., granulomatous disease) should be considered.¹⁸

CLUBBING

Digital clubbing may be present in up to 50% of patients with IPF.^5-7

Clubbing is commonly seen in other pulmonary diseases, including lung cancer and pulmonary tuberculosis, as well as in congestive heart failure.¹⁹

Source: National Heart, Lung, and Blood Institute, National Institutes of Health.

Available at https://www.nhlbi.nih.gov/health/idiopathic-pulmonary-fibrosis/diagnosis.

Accessed August 28, 2017.²⁰

PULMONARY FUNCTION TESTING

Patients with suspected IPF should undergo full pulmonary function testing.²¹

• Spirometry
• Complete lung volume assessment
  • Total lung capacity (TLC)
  • Forced vital capacity (FVC)
  • Forced expiratory volume in 1 second (FEV₁)
• Evaluation of diffusing capacity of carbon monoxide (DL_CO)

Patients with IPF generally show reduced total lung capacity. TLC generally decreases in IPF because parenchymal scar tissue accumulates, resulting in reduced intrinsic elasticity and subsequent distortion of normal lung architecture.³

Patients with IPF often show a restrictive pattern on spirometry.³

Restrictive defect:

• TLC is low
• Low FVC
• Higher FEV₁/FVC ratio
• Flows are higher than expected at a given lung volume

Obstructive defect:

• TLC is normal
• Normal FVC but lower FEV₁
• Lower FEV₁/FVC ratio
• Flows are lower than expected over the entire volume range

Used with permission from Pellegrino R et al. Eur Respir J. 2005;26(5):948-968.⁴

Patients with IPF also tend to have impaired gas exchange. Fibrosis during IPF affects how well the lungs exchange gases, which can be seen by measuring the diffusion capacity of the lungs, particularly carbon monoxide (DL_co).³

Reduced DL_co may occur before reduced lung volumes, and can be found during the early stages of IPF.⁷

In patients with concomitant IPF and emphysema, spirometric measures and lung volumes may be normal, but DL_co will invariably be low.^22,23

Most patients with IPF will experience hypoxemia on exertion.³ Patients may or may not show decreased blood gas exchange/oxygen saturation at rest.³

OTHER CLINICAL EVALUATIONS

Patients with IPF or suspected IPF should have a cardiovascular workup.

• Pulmonary hypertension is a common comorbidity in IPF²⁴
• Patients with IPF or suspected IPF should be evaluated for potential pulmonary vascular abnormalities, such as right ventricular hypertrophy or right bundle branch block patterns²⁵

Patients should be evaluated for signs and symptoms of CTD.

The ATL/ERS/JRS/ALAT 2018 guidelines recommend evaluating patients with suspected IPF for:¹

• Rheumatoid factor
• Anti-cyclic citrullinated peptide (CCP)
• Anti-C-reactive protein (CRP)
• Anti-nuclear antibody (ANA) titer and pattern
• Others on a case–by–case basis

Patients with interstitial lung disease (ILD) and clinical signs or symptoms that meet the diagnostic criteria for CTD do not have IPF.¹

Other tests should be ordered based on the patient’s specific symptoms.

Possible symptoms and associated tests include:^2,26-28

High titers of autoantibodies suggest the presence of CTD.⁸

Approximately 10%-20% of patients with IPF have low-level titers of ANA (<1:160) or rheumatoid factor.⁸

• Such patients should be screened for signs and symptoms of CTD (e.g., arthritis, Raynaud's phenomenon, skin changes, abnormal esophageal motility)²

Patients with suspected CTD but low titers should be retested.

If CTD is strongly suspected but the tests do not show strong evidence of CTD, the panel may be repeated after initial testing.^2,29

MEDICAL HISTORY

A detailed medical history is essential to diagnosing IPF.

In all cases of potential ILD, a detailed medical history should be taken that covers:^1,2

• Comorbidities
• Social history
• Occupational and environmental exposures
• Drug exposures
• Family history

IPF has several common comorbidities.

Common comorbidities seen with IPF include:²⁴

• GERD
• Emphysema
• Coronary artery disease
• Congestive heart failure
• Obstructive sleep apnea
• Pulmonary hypertension, either due to chronic hypoxia or as a result of ILD
• Lung cancer

Many patients are former smokers at the time of IPF diagnosis.^5,30 Cigarette smoking is strongly associated with IPF, especially among patients with a history of smoking more than 20 pack-years.³⁰

Certain occupational and environmental exposures are associated with IPF.

Occupational and environmental exposures that are associated with increased risk of IPF include:³¹

• Varied sources of dust and/or particulate matter
• Agriculture-related and livestock-related exposures
• Raising birds

Although these exposures are associated with IPF, they have not been found to be causative.³²

IPF and Hypersensitivity Pneumonitis.

IPF can look like hypersensitivity pneumonitis (HP) but differs by environmental exposures.

• HP is typically caused by an inflammatory reaction to inhaled organic particles³³
• Specific fungi:³³
  • Bird feathers (e.g., household bedding)
  • Atypical mycobacterium (e.g., those that colonize hot tubs)

It is essential to distinguish between IPF and HP.

• The workup and treatment for IPF and HP are vastly different^33,34
• HP is treated with systemic corticosteroids,³³ which is strongly discouraged when treating IPF²

Serologic workup should be performed for suspected cases of HP.

Patients whose exposure history suggests HP should undergo a serologic workup including fungal antigen panels and immunoglobulin G levels toward the suspected offending antigen.³³

Numerous drugs have been associated with development of ILD.^35,36

The website Pneumotox is freely available and accessible to help in diagnosing potential drug-induced ILD by drug name or pathologic condition.³⁵

Family History

Family history of IPF or young age should lead to suspicion of familial IPF.

• Familial IPF is generally indistinguishable from sporadic cases based on clinical and/or histologic characteristics^37,38

Both familial and sporadic cases of IPF have been linked with genetic mutations^39-42