Idiopathic%20pulmonary%20fibrosis Diagnosis
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
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
History
- 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)
Physical Examination
- 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
Laboratory Tests
- 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)
- Antinuclear antibodies (ANA) or rheumatoid factor titers are not that high & are positive in about 30% of patients with idiopathic pulmonary fibrosis
- 6-minute walk test (6MWT)
- A marker of functional exercise capacity
- Used as an initial & longitudinal clinical assessment for patients with idiopathic pulmonary fibrosis
Imaging
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
Screening
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
- All 3 features:
- 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 (DLCO)
- A decrease in DLCO may precede with the development of abnormal lung volumes
- DLCO is greatly reduced in patients with idiopathic pulmonary fibrosis
- Strong predictors of increased mortality:
- Progressive decline in DLCO (>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
Acute Exacerbation of Idiopathic Pulmonary Fibrosis
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, DLCO & 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