Idiopathic%20pulmonary%20fibrosis Diagnosis

Diagnostic Criteria for Idiopathic Pulmonary Fibrosis

• Establishing diagnosis involves clinical, radiological, & pathological correlation
• Includes the following:
  
  • Other causes of interstitial lung disease have been excluded
  • Usual interstitial pneumonia pattern confirmed with high-resolution computed tomography (HRCT) without biopsy (see HRCT criteria on Imaging section)
  • HRCT & histopathologic criteria confirms usual interstitial pneumonia pattern after surgical lung biopsy (see histopathological criteria on Screening section)

Classification of Idiopathic Interstitial Pneumonia (IIP)

• Based on the consensus statement of the American Thoracic Society (ATS) & European Respiratory Society (ERS)
• Major idiopathic interstitial pneumonia:
  
  • Idiopathic pulmonary fibrosis - most common
  • Idiopathic nonspecific interstitial pneumonia
  • Respiratory bronchiolitis-associated interstitial pneumonia
  • Desquamative interstitial pneumonia
  • Cryptogenic organizing pneumonia
  • Acute interstitial pneumonia 

• Rare idiopathic interstitial pneumonia:
  
  • Idiopathic lymphoid interstitial pneumonia
  • Idiopathic pleuroparenchymal fibroelastosis 

• Unclassifiable idiopathic interstitial pneumonia

• Since symptoms of idiopathic pulmonary fibrosis are nonspecific, having a complete history is essential as it excludes other causes of interstitial lung diseases
• A complete history should include:
  
  • Medications like Amiodarone, Bleomycin, Nitrofurantoin are associated with pulmonary fibrosis
  • Recreational or drug use
  • Occupational exposure (eg asbestos, silica, heavy metals, contaminated ventilation systems, moldy foliage, &/or pigeon droppings)
  • Environmental respiratory exposure
  • Human immunodeficiency (HIV) infection
  • Review of systems - presence of arthralgia, photosensitivity, arthritis, dry eyes &/or mouth, Raynaud phenomenon must be checked to ensure that other causes of interstitial lung diseases (ILD) are excluded
  • Current smoker
  • Social 

• Patients should also be asked for the presence of obstructive sleep apnea (OSA)

• Prominent findings in patients with idiopathic pulmonary fibrosis :
  
  • Fine bibasilar inspiratory crackles (known as Velcro crackles)
  • Digital clubbing
  • 20-40% of patients have pulmonary hypertension at rest & is a common comorbidity
    
    • Loud P2 component of the 2nd heart sound, fixed split S2, holosystolic tricuspid regurgitation murmur & pedal edema are present
  • Right ventricular hypertrophy may be observed
    
    • Right ventricular heave is palpated at the lower left sternal border
    • Right atrial pressure is increased & causes an increase in jugular venous pressure

• Routine laboratory studies are nonspecific in diagnosing idiopathic pulmonary fibrosis
• The following are some tests that excludes other interstitial lung diseases:
  
  • Antinuclear antibodies (ANA) or rheumatoid factor titers are not that high & are positive in about 30% of patients with idiopathic pulmonary fibrosis
    
    • High titers are suggestive of connective tissue diseases
  • Elevated C-reactive protein level & erythrocyte sedimentation rate (ESR)
    
    • May be elevated but is nondiagnostic of idiopathic pulmonary fibrosis
  • Complete blood count (CBC) may reveal polycythemia & is rare in patients with idiopathic pulmonary fibrosis
  • Chronic hypoxemia is a common finding in arterial blood gas (ABG)

• 6-minute walk test (6MWT)
  
  • A marker of functional exercise capacity
  • Used as an initial & longitudinal clinical assessment for patients with idiopathic pulmonary fibrosis

Chest Radiography

• Typical findings are a net-like linear & curvilinear densities or peripheral reticular opacities that can be found at lung bases
• May also reveal honeycombing or loss of lower lobe volume
• Not a diagnostic test for patients with idiopathic pulmonary fibrosis as it lacks specificity
• Usually, all patients who present with idiopathic pulmonary fibrosis at the time of diagnosis have an abnormal chest X-ray findings

High-Resolution Computed Tomography (HRCT) Scanning

• Essential & more sensitive & specific
• Reveals a patchy, peripheral, subpleural & bibasilar reticular opacities in patients with idiopathic pulmonary fibrosis
• Criteria for usual interstitial pneumonia pattern (all 4 features should be present):
  
  • Subpleural, basal predominance is present
  • With reticular abnormality
  • Evidence of honeycombing with or without traction bronchiectasis
  • Absence of features listed as inconsistent with usual interstitial pneumonia pattern 

• Possible usual interstitial pneumonia pattern (all 3 features should be present):
  
  • Subpleural, basal predominance is present
  • With reticular abnormality
  • Absence of features listed as inconsistent with usual interstitial pneumonia pattern 

• Inconsistent usual interstitial pneumonia pattern (any of the 7 features should be present):
  
  • Upper or mid-lung predominance is present
  • Peribronchovascular predominance is present
  • With extensive ground-glass abnormality (extent greater than reticular abnormality)
  • Has profuse micronodules (bilateral, predominantly located in the upper lobes)
  • With discrete cysts (multiple, bilateral, away from areas of honeycombing)
  • Evidence of diffuse mosaic attenuation or air-tapping (bilaterally, in ≥3 lobes)
  • With consolidation in bronchopulmonary segments or lobes

Transthoracic Echocardiography

• Used to detect pulmonary hypertension
  
  • Approximately 20-40% of idiopathic pulmonary fibrosis patients who are candidates for lung transplantation have pulmonary hypertension at rest 

• Pulmonary hypertension is defined as the mean pulmonary artery pressure of >25 mmHg at rest with normal capillary wedge pressure
• Measured by using a right-sided heart catheterization

Other Procedures

Bronchoalveolar Lavage (BAL)

• Used to exclude other alternative diagnosis
• Eosinophilia & lymphocytosis may be evident in bronchoalvelolar lavage fluid
• Presence of neutrophilia in bronchoalveolar lavage fluid predicts early mortality
• Appropriate analysis of bronchoalveolar lavage may reveal infection, malignancy, alveolar proteinosis, eosinophilic pneumonia, or occupational dusts
• Based on the studies of bronchoalveolar lavage matrix metalloproteinase (MMP), both MMP 1 & MMP 7 are increased in patients with idiopathic pulmonary fibrosis, with MMP 7 is associated with disease severity

Bronchoscopy

• Transbronchial biopsy &/or bronchoscopy with bronchoalveolar lavage are not required for the diagnosis of idiopathic pulmonary fibrosis
• Ensures that alternative diagnosis are excluded

Histopathology

• The associated histopathological lesion is usual interstitial pneumonia (UIP)
  
  • A heterogenous, variegated appearance with alternating areas of healthy lung, interstitial inflammation, fibrosis & honeycomb (patchwork appearance) on low magnification 

• Specimens taken during an acute exacerbation of idiopathic pulmonary fibrosis revealed:
  
  • Combination of usual interstitial pneumonia with superimposed diffuse alveolar damage
  • Alveolar septa are expanded by more extensive fibroblast proliferation
  • Marked hyperplasia of type 2 pneumocytes
  • Remnants of hyaline membrane are present  

• The usual interstitial pneumonia pattern may be associated with other diseases such as asbestosis, collagen-vascular disease, sarcoidosis, hypersensitivity pneumonitis, or toxic drug reactions (eg Amiodarone, Bleomycin, Nitrofurantoin)
• Criteria for usual interstitial pneumonia pattern (all 4 features should be present):
  
  • Marked fibrosis or architectural distortion &/or honeycombing in predominantly subpleural or paraseptal distribution is evident
  • Patchy involvement of the lung parenchyma by fibrosis is present
  • Fibroblast foci is present
  • Features against a diagnosis of usual interstitial pneumonia suggesting an alternate diagnosis are absent 

• Probable usual interstitial pneumonia pattern requires:
  
  • All 3 features:
    
    • Marked fibrosis or architectural distortion &/or honeycombing should be present
    • Either the patchy involvement or fibroplastic foci, but not both should be absent
    • The features against a diagnosis of usual interstitial pneumonia that suggests an alternate diagnosis should be absent
  • Or:
    
    • Only honeycombing changes 

• Possible usual interstitial pneumonia pattern (all 3 criteria should be present):
  
  • Presence of patchy or diffuse involvement of lung parenchyma by fibrosis, with or without interstitial inflammation
  • Other criteria for an usual interstitial pneumonia are absent
  • The features against a diagnosis of usual interstitial pneumonia that suggests an alternate diagnosis is absent 

• Non-UIP pattern (any of the 6 criteria may be present):
  
  • Hyaline membranes
  • Organizing pneumonias
  • Granulomas
  • Marked interstitial inflammatory cell infiltrate away from honeycombing
  • Predominant airway centered changes
  • Other features suggestive of an alternate diagnosis 

Surgical Lung Biopsy

• May be done via open lung biopsy (OLB) or video-assisted thoracoscopic surgery (VATS)
  
  • Video-assisted thoracoscopic surgery is more preferred because it is associated with less morbidity & shorter duration of stay in the hospital 

• May be considered in patients with possible usual interstitial pneumonia or inconsistent with usual interstitial pneumonia pattern on high-resolution computed tomography

Other Tests

Pulmonary Function Tests (PFTs)

• A noninvasive quantitative measurement
• The keystone in the assessment of disease progression & its severity
• Results of pulmonary function tests in patients with idiopathic pulmonary fibrosis:
  
  • Presence of restrictive ventilatory defect
  • Reduced diffusion capacity for carbon monoxide
  • Decreased functional residual capacity (FRC), vital capacity (VC), total lung capacity (TLC), & forced vital capacity (FVC) & forced expiratory volume in 1 second (FEV₁)
    
    • Prognostication relies on the serial assessment of FVC
    • The risk of mortality increases if there is a decline of >10% in FVC over 6 months
  • Increased FEV₁/FVC ratio associated with hypoxemia & dyspnea in patients 60-70 years old 

• Obstructive ventilatory defects are uncommon
  
  • If present, it may coexist with chronic obstructive pulmonary disease (COPD) 

• Impaired gas exchange is demonstrated by:
  
  • Decreased diffusion capacity for carbon monoxide (DL_CO)
  • A decrease in DL_CO may precede with the development of abnormal lung volumes
  • DL_CO is greatly reduced in patients with idiopathic pulmonary fibrosis

• Strong predictors of increased mortality:
  
  • Progressive decline in DL_CO (>15% after 6 months)
  • Desaturation of <88% during a 6-minute walk test (6MWT)
  • Failure of the heart rate to decline in 1-2 minutes post-exercise

Diagnostic Criteria

• Confirmed diagnosis of idiopathic pulmonary fibrosis
• Unexplained worsening of dyspnea within a month
• Hypoxemia
• New alveolar abnormality in imaging studies
• Absence of other etiologies such as infection, pulmonary embolism, pneumothorax, cardiac failure

Pathophysiology

• Clinical similarities with acute distress syndrome:
  
  • Need for increased oxygen
  • Presence of bilateral ground glass opacities &/or consolidation on imaging
  • Findings of diffuse alveolar damage on histopathology 

• Lung injuries that would develop into an acute exacerbation of idiopathic pulmonary fibrosis:
  
  • Microaspiration of gastric contents
  • Surgery & other procedures (eg surgical lung biopsy, lung cancer resection & bronchoscopy)
  • With decreased FVC, DL_CO & 6-minute walk test (6MWT)

• Other potential contributors include evidence of pulmonary hypertension & coronary artery disease (CAD), higher body mass index (BMI), & treatment using immunosuppressive therapy

Signs & Symptoms

• Shortness of breath
• Exercise intolerance
  
  • May develop over days to weeks but not >1 month 

• Cough with or without production of sputum (common)
• Fever
• Flu-like symptoms