Common misconceptions and mistakes
- •
Bronchoscopy with transbronchial biopsies are usually indicated and helpful in the evaluation of diffuse parenchymal lung disease
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Video-assisted thoracoscopic surgery (VATS) lung biopsy is always required to confirm the diagnosis of usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF)
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Bronchial alveolar lavage is always the initial step in the evaluation of diffuse parenchymal lung disease (DPLD)
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Prematurely celebrating a steroid response in a patient with hypoxemic respiratory failure secondary to DPLD
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Advising a patient with respiratory failure and DPLD to be do not intubat (DNI) because they “will never be able to be extubated”
Diffuse Parenchymal Lung Disease
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Describes a diverse group of conditions that share the common pathologic feature of diffuse interstitial and/or alveolar inflammation, cellular infiltration, and/or fibrosis
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Fibrosis may exist alone, as in UIP, or with an inflammatory cellular infiltrate, as in nonspecific interstitial pneumonia (NSIP)
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The radiographic patterns exist on a spectrum from specific—as in UIP, where a “definite UIP” scan can obviate the need for biopsy—to diffuse ground glass (broad differential)
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Several DPLD entities have classic, characteristic CT scan patterns (eg, chronic eosinophilic pneumonia [CEP], cryptogenic organizing pneumonia [COP], respiratory bronchiolitis-associated interstitial lung disease/desquamative interstitial pneumonia [RB-ILD/DIP]), recognition of which is key to appropriate evaluation and management
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The clinical presentations are diverse and can be broadly divided into three categories:
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Asymptomatic
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Incidental finding in chest x-ray films and/or CT imaging
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Subacute
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Progressive dyspnea on exertion (weeks to months)
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Often with cough, night sweats, and fatigue
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Pulmonary function tests (PFTs) show restriction with a reduced diffusing capacity of the lung for carbon monoxide (DLCO) (may show isolated low DLCO initially)
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Acute hypoxemic respiratory failure (days to weeks)
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Often progresses over days
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May require 100% O 2 (high flow), bilevel positive airway pressure (BiPAP), or mechanical ventilation with high positive end-expiratory pressure (PEEP)
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In the case of an acute exacerbation of UIP/IPF, it is often fatal
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Cardiogenic pulmonary edema (ie, heart failure) and atypical pneumonia (eg, pneumocystis jiroveci pneumonia [PJP], nontuberculous mycobacteria [NTM], viral) are important, common mimics
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Presumptive diagnosis of DPLD requires integrating the clinical presentation with the CT scan radiographic pattern
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Often made after empirically treating and/or ruling out heart failure and atypical pneumonia
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Definitive diagnosis often requires a lung biopsy (not always practical or feasible) and a compatible clinical scenario
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Adequate biopsy requires VATS, with multiple areas sampled (avoiding clearly fibrotic “burned out” areas)
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Patients with fibrosis are at high risk for developing a persistent BP fistula after VATS, leading to:
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Prolonged hospitalization (initially tethered to suction)
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Discharge from the hospital with a chest tube and one-way valve (eg, Heimlich)
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Occasionally patients experience accelerated fibrosis after VATS, leading to refractory/persistent hypoxemic respiratory failure, necessitating terminal extubation
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The role of bronchoscopy in diffuse parenchymal lung disease is to:
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Rule out atypical infection (mainly):
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PJP
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NTM
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Viral pneumonia (via polymerase chain reaction [PCR] testing)
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Make the diagnosis of:
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Diffuse alveolar hemorrhage (DAH)
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Progressively bloodier alveolar lavage
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- •
Acute and chronic eosinophilic pneumonia
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Bronchoalveolar lavage (BAL) eosinophilia > 25% (often > 60% in CEP)
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Sarcoidosis (via endobronchial ultrasound–guided transbronchial needle aspiration)
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Noncaseating granuloma, with no organism or material identified
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Lymphangitic spread of tumor (via transbronchial biopsy)
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Malignant cells identified by surgical pathology
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Pulmonary alveolar proteinosis
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Periodic acid shift (PAS) positive; milky, granular fluid recovered at BAL
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Support the diagnosis of:
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Cryptogenic organizing pneumonia
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> 25% lymphocyte cell count by BAL
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Acute interstitial pneumonia
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> 25% (often > 60%) neutrophil count by BAL
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Pulmonary Langerhans cells
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CD1a-positive Langerhans (> 5%) cells
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Diagnostic and therapeutic approaches to diffuse parenchymal lung disease hinge on integrating the clinical presentation and CT scan pattern ( Table 17.1 )
Table 17.1
Restrictive Pattern on Pulmonary Function Testing (PFT)
CT Scan Pattern / Predominant Finding
Clinical Presentation
Asymptomatic
Incidental Finding
Subacute Presentation
Progressive DOE ± Dry Cough
Acute Presentation
Hypoxemic Respiratory Failure
Usual Interstitial Pneumonia (UIP) Pattern:
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Diffuse Subpleural Reticular Infiltrate
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Lower lobe predominance
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≥ 2 rows of ‘Honey Combing’
- •
Traction Bronchiectasis
Minimal or NO: Ground Glass, Nodules, Cysts, Adenopathy
Idiopathic Pulmonary Fibrosis (i.e. UIP)
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Drug Induced
- •
Connective tissue disease related
Pneumoconiosis
Post- Inflammatory
Idiopathic Pulmonary Fibrosis (i.e. UIP)
- •
Drug Induced
- •
Connective tissue disease related
Pneumoconiosis
Idiopathic Pulmonary Fibrosis (i.e. UIP)
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Drug Induced
- •
Connective tissue disease related
Non-specific Interstitial Pneumonia Pattern:
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Multifocal Ground Glass Opacities
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Scattered Subpleural Reticular Infiltrate
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Traction Bronchiectasis
Minimal or NO: Honeycomb Cysts
Non-specific Interstitial Pneumonia
- •
Drug Induced
- •
Connective Tissue Disease associated
Pneumoconiosis
Non-specific Interstitial Pneumonia
- •
Drug Induced
- •
Connective Tissue Disease associated
Pneumoconiosis
Chronic Hypersensitivity Pneumonitis (upper lobe)
Non-specific Interstitial Pneumonia
- •
Drug Induced
- •
Connective Tissue Disease associated
Acute Hypersensitivity Pneumonitis (upper lobe)
Ground Glass Opacities alone
Respiratory Bronchiolitis-associated ILD
Simple Pulmonary Eosinophilia
Desquamative Interstitial Pneumonia
Pneumocystis Jiroveci Pneumonia
Respiratory Bronchiolitis-associated ILD
Simple Pulmonary Eosinophilia
Acute Respiratory Distress Syndrome
Cardiogenic Pulmonary Edema (effusions)
Diffuse Alveolar Hemorrhage
Pneumocystis Jiroveci Pneumonia
Ground Glass Opacities with Dense Consolidations ± Traction Bronchiectasis
Cryptogenic Organizing Pneumonia (Reverse Halo)
Nontuberculous Mycobacteria (Tree & Bud)
Chronic Aspiration
Cryptogenic Organizing Pneumonia (Reverse Halo)
Chronic Eosinophilic Pneumonia (peripheral)
Nontuberculous Mycobacteria (Tree & Bud)
Acute Eosinophilic Pneumonia
Acute Interstitial Pneumonia
Acute Respiratory Distress Syndrome
Cardiogenic Pulmonary Edema (effusions)
Cryptogenic Organizing Pneumonia (Reverse Halo)
Severe Bacterial Pneumonia
Nodules (Bronchovascular & Perilymphatic) with:
- •
Hilar and mediastinal adenopathy
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Conglomerate masses / Dense consolidations
- •
± Ground Glass
Sarcoidosis Stage II – III
Lymphangitic / Metastatic Spread of Tumor
Sarcoidosis Stage II – III
Lymphangitic/ Metastatic Spread of Tumor
Sarcoidosis Stage II – III
Lymphangitic/ Metastatic Spread of Tumor
Nodules (Centrilobular)
Nontuberculous Mycobacteria (Tree & Bud)
Early Pulmonary Langerhans (Cavitary)
Nontuberculous Mycobacteria (Tree & Bud)
Early Pulmonary Langerhans (Cavitary )
*****************************************
Crazy Paving
Alveolar Proteinosis
Alveolar Proteinosis
Cardiogenic Pulmonary Edema
Lymphangitic Spread of Tumor
Cardiogenic Pulmonary Edema (effusions)
Viral Pneumonia
Cysts
Lymphocytic Interstitial Pneumonia
Lymphocytic Interstitial Pneumonia
Lymphangioleiomyomatosis
Late Pulmonary Langerhans (large, thicker walled)
Lymphocytic Interstitial Pneumonia
Lymphangioleiomyomatosis
Obstructive or Mixed Obstructive Restrictive Pattern on PFT
CT Scan Pattern / Predominant Finding
Clinical Presentation
Asymptomatic
Incidental Finding
Subacute Presentation
Progressive DOE ± Dry Cough
Acute Presentation
Respiratory Failure
Ground Glass opacities alone
Respiratory Bronchiolitis-associated ILD
Respiratory Bronchiolitis-associated ILD
Cardiogenic Pulmonary Edema (effusions)
Nodules (Bronchovascular & Perilymphatic) with:
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Hilar and mediastinal adenopathy
- •
Conglomerate masses / Dense consolidations
- •
± Ground Glass
Sarcoidosis (Stage II – III)
Sarcoidosis (Stage II – III)
Sarcoidosis (Stage II – III)
Mosaicism from Air Trapping ( Tree & Bud)
Bronchiolitis Obliterans
Bronchiolitis Obliterans
Bronchiolitis Obliterans
Diffuse Cysts
Lymphangioleiomyomatosis
Lymphangioleiomyomatosis
Lymphangioleiomyomatosis
Cavitary Nodules and Large Cysts
Pulmonary Langerhans
Pulmonary Langerhans
*****************************************
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Asymptomatic Diffuse Parenchymal Lung Disease Pattern Incidentally Found by Chest CT Imaging
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PFTs are normal, mildly restricted, or show an isolated low DLCO
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Chest CT scan suggests:
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Definite to possible UIP, NSIP, or hypersensitivity pneumonitis (HP)
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Classic imaging features shared by all three entities ( Fig. 17.1 ):
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Diffuse subpleural reticular infiltrate
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Ground-glass opacities
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Traction bronchiectasis
Fig. 17.1
Cropped chest computed tomography (CT) images of patients with diffuse parenchymal lung disease (and/or mimics), showing the most commonly seen types of opacities. (A) The opacities commonly seen in usual interstitial pneumonia, specifically a diffuse subpleural reticular infiltrate, basilar honeycombing, and traction bronchiectasis. (B) Both multifocal and diffuse ground-glass opacities are commonly seen in nonspecific interstitial pneumonia and mimics, like atypical infection, cardiogenic edema, and alveolar hemorrhage. (C) Mosaicism describes the juxtaposition of areas of increased attenuation with areas of decreased attenuation. The challenge is to establish whether the lower attenuation lung represents normal parenchyma, and the higher attenuation lung ground glass opacities, or whether the higher attenuation lung represents normal parenchyma and the lower attenuation lung represents disease; either trapped air (as seen in asthma with active bronchospasm or bronchiolitis obliterans) or decreased perfusion (as seen in chronic thromboembolic disease). Air trapping is demonstrated during expiratory CT imaging, which shows that the areas of decreased attenuation in the inspiratory film remain dark, whereas the areas of normal lung attenuation become whiter. If, on the other hand, the areas of decreased attenuation whiten with exhalation, then the low attenuation areas are normal, and the areas of increased attenuation on the inspiratory film actually represent ground glass. (D) Diffuse cysts (as seen in lymphangiomyomatosis and lymphocytic interstitial pneumonia) and crazy paving (as seen in cardiogenic edema, atypical infection, lymphangitic spread of tumor, and alveolar proteinosis). (E) Multiple nodules in varying distributions (as seen in granulomatous disease and atypical lung infection).
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- •
Diagnostic workup involves a clinical and/or immunologic screen for:
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Hypersensitivity (eg, farmer’s lung) and pneumoconiosis (eg, asbestosis)
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Query exposures to birds, asbestos, silica, and environments that produce (or have produced in the past) respiratory symptoms for the patient
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Check a hypersensitivity panel
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Connective tissue disease
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Examination for skin, muscle, and joint disease
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Serology for RF, ANA, and ESR
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Medications associated with DPLD (eg, Amiodarone, biologics, methotrexate, chemotherapeutics)
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A history of inhalation injuries (eg, chlorine fumes) or acute respiratory distress syndrome (ARDS)
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Cigarette smoking
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Management:
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Serial PFTs and clinical screen for symptoms (± imaging)
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Every 3–12 months based on concern (pattern and extent of disease) until 3–5 years of stability is demonstrated
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Advise avoidance of environments that produce respiratory symptoms
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Advise bird fanciers to get rid of their birds (surprisingly difficult and/or impossible)
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The allergy can be to thermophilic bacteria that live in the bird guano such that individuals may be exposed via bird droppings on a balcony or window ledge
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Individuals with a positive physical or immunologic screen for connective tissue disease should be evaluated by rheumatology
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Stop any and all possible inciting medications
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These are not appropriate drugs for an individual with a DPLD pattern on by imaging
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Smokers should be aggressively counseled about cessation
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Nontuberculous mycobacteria (NTM) ( Fig. 17.2 )
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Special features:
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NTM are ubiquitous in soil and water, with infection occurring after inhalation, commonly during showering
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Predilection for individuals with a long, thin thorax (same phenotype as primary spontaneous pneumothorax [PTX])
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- •
Classic imaging features:
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Tree and bud nodules
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Airway-associated consolidations and ground-glass opacities
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Areas of dense consolidation accompanied by traction bronchiectasis and volume loss
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Classically involving the right middle lobe
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Subcentimeter nodules and/or calcified granuloma are also common
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Diagnostic workup involves screening for symptoms—mainly productive cough, weight loss, and night sweats
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If the patient has a productive cough, send at least three specimens for acid-fast bacilli (AFB) stain and culture
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Management involves serial PFTs, a clinical screen for symptoms, and imaging
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Every 3–12 months based on concern (extent of disease on imaging) until 3–5 years of stability is demonstrated
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Stability in NTM may be interpreted as waxing and waning nodules as long as there is no net increase in parenchymal destruction and bronchiectasis over time
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Fig. 17.2
(A) Computed tomography (CT) imaging of a patient with nontuberculous mycobacteria (NTM) infection. Multiple centrilobular nodules can be seen existing on a size spectrum, from micronodules in a tree and bud distribution (≤ 5 mm), to ground-glass nodules (5 mm to 1 cm), to solid nodules > 1 cm. There are also small peripheral dense consolidations in the left upper lobe with traction bronchiectasis. (B) A different patient with NTM and classic involvement/destruction of the right middle lobe with dense consolidation, volume loss, traction bronchiectasis, and tree and bud nodules.
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Chronic aspiration ( Fig. 17.3 )
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Special features:
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Associated with sedative/hypnotic use at bedtime
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Classic imaging features:
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Dynamic basilar/dependent dense consolidations and ground-glass opacities
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Nonspecific areas of fibrosis
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- •
Diagnostic workup involves screening for gastroesophageal reflux disease (GERD) symptoms, choking on food, and/or nocturnal arousals associated with forceful coughing/choking episodes
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Management involves:
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Proton pump inhibitor and treating reflux maximally if present (eg, elevation of the head of the bed, diet modification)
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Screen for, and advise against, the use of sedative and/or alcohol use at bedtime (explain the importance of falling asleep vs passing out)
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Antibiotics covering oral anaerobes should be used in most situations
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The presence of an air fluid level within a consolidation is worrisome for necrosis (ie, lung abscess), which requires 1–3 months of oral anaerobic coverage until the air fluid level resolves
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Occasionally, preexisting bullae partially fill with infected/inflammatory material, mimicking a lung abscess ( CH 11 )
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- •
Short-interval serial imaging and clinical follow-up:
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Chest x-ray every 1–3 months, anticipating complete resolution of ground-glass and dense consolidations
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Occasionally, new opacities appear as old ones resolve, necessitating continued imaging and interventions aimed at reducing aspiration
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Any residual/persistent x-ray opacities should be evaluated by CT scan to ensure all findings are compatible with scarring (and not worrisome for malignancy)
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Fig. 17.3
(A) The initial computed tomography (CT) scan of a 48-year-old smoker who was incidentally found to have an abnormal chest x-ray and follow-up CT scan demonstrating a dense right upper lobe consolidation with right middle lobe ground glass and focal subpleural reticular scarring (sparing the base). The patient was treated with clindamycin for 1 month, and a repeat CT scan was obtained. (B) Follow-up CT scan (6 weeks later) demonstrating improvement in the right upper and middle lobes, with a new dense right lower lobe consolidation and possible abscess vs preexisting emphysematous hole. Further questioning of the patient revealed his nightly use of chlorohydrate for insomnia. The patient’s recurrent aspiration resolved after chlorohydrate was discontinued.
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Stage II and/or III sarcoidosis ( Fig. 17.4 )
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Special features:
- •
Affects African Americans more than Caucasians and women more than men
- •
Common symptoms include cough and shortness of breath ± pleuritic chest pain
- •
The majority of the time, pulmonary sarcoidosis runs its course (and remits) irrespective of therapy
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~ 50% in 3 years, ~ 75% within 10 years
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- •
Recurrence after 1 year of remission is rare (< 5%)
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Nodular sarcoidosis progresses to a fibrotic pattern in 20–25% of cases (regardless of therapy)
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Fibrotic progression is most common in poor African Americans who suffer disease onset later in life
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- •
- •
Classic imaging features:
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Bilateral hilar and mediastinal lymphadenopathy
- •
Bronchovascular and perilymphatic micronodules, often coalescing into
- •
Macro nodules and dense consolidations
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- •
Ground-glass opacities
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Scattered areas of subpleural reticular change
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- •
Diagnostic workup involves:
- •
PFTs
- •
May show restriction or mixed obstructive-restrictive disease, with a decreased DLCO
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- •
Chronic granulomatous disease immunologic screen:
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Interferon gamma release assay testing for TB exposure
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Antigen/antibody testing for endemic fungal infection
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- •
Endobronchial ultrasound-guided transbronchial needle aspiration of any hilar and/or mediastinal lymphadenopathy
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Transbronchial lung biopsies should be performed in the absence of adenopathy (also high yield)
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Management involves serial PFTs, clinical screen for symptoms, and ± imaging
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Every 3–12 months based on concern (extent of disease on imaging) until 3–5 years of stability is demonstrated
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Fig. 17.4
(A) Bilateral paratracheal, hilar, and subcarinal adenopathy. The small size of the hilar adenopathy suggests stage III sarcoid (smaller from the previous scan [not shown]). (B) Classic parenchymal changes associated with stage II – III sarcoidosis—namely diffuse micronodules in a bronchovascular and perilymphatic distribution, coalescing into areas of dense consolidation, with multifocal ground-glass opacities.
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Respiratory bronchiolitis-associated ILD/desquamative interstitial pneumonia ( Fig. 17.5 )
- •
Special features:
- •
Active smokers
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- •
Classic imaging features:
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Diffuse ground-glass opacities
- •
Often faint/subtle
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- •
- •
Diagnostic workup involves screening for active tobacco use
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In the absence of tobacco use, individuals should be treated like suspected HP/NSIP
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Early HP and NSIP may be hard to distinguish form RB-ILD/DIP (but are more likely to cause symptoms)
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- •
Management:
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Smokers should be aggressively counseled about cessation
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They should be informed that they have a relatively unusual allergy to cigarette smoke (unlike most people who only need to fear COPD and lung cancer) and that they are actively scarring their lungs
- •
Patients should leave the office with a prescription for smoking cessation therapy (emphasizing the medical necessity of quitting)
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- •
- •
Serial PFTs, clinical screen for symptoms, and ± imaging
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Every 3–12 months based on concern (pattern and extent of disease on imaging) until 3–5 years of stability is demonstrated
- •
- •
Nonsmokers are managed like suspected HP/NSIP
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Fig. 17.5
Computed tomography (CT) imaging of the chest reveals a subtle, diffuse, ground-glass opacification, with probable areas of air trapping (no expiratory imaging available for conformation), in a smoker with a chronic cough and no change in exercise ability. Pulmonary function tests showed mixed obstructive-restrictive disease with a mildly decreased diffusing lung capacity for carbon monoxide. The clinical radiographic scenario is very suggestive of respiratory bronchiolitis-interstitial lung disease.
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- •
Subacute Dyspnea On Exertion with a Diffuse Parentchymal Lung Disease Pattern Found on by Chest CT Imaging
- •
PFTs show a restrictive pattern, with a reduced DLCO or an isolated low DLCO
- •
Patients may complain of a dry cough and/or systemic symptoms (eg, fevers, night sweats)
- •
Patients with DPLD, dyspnea, and restrictive PFTs deserve a screen for desaturation with exercise if they demonstrate any of the following:
- •
Resting O 2 saturation < 95% on RA
- •
Moderately to severely reduced DLCO
- •
Severe exercise limitation
- •
- •
Chest CT scan suggests:
- •
Definite UIP ( Fig. 17.6 )
- •
Special features:
- •
Idiopathic disease of polyclonal fibroblast proliferation in the pulmonary interstitium
- •
Leads to progressive respiratory failure from hypoxemia and restrictive physiology
- •
Median survival of 3 years
- •
- •
Tends to progress in a stepwise fashion with times of stable disability punctuated by episodes of precipitous decline
- •
Often in the setting of, or triggered by, a respiratory infection
- •
- •
A rare familial form also exists
- •
- •
Classic imaging features:
- •
Diffuse subpleural reticular infiltrate
- •
Lower-lobe predominance
- •
Greater than or equal to two rows of “honeycombing” (ie, architectural distortion)
- •
Traction bronchiectasis
- •
Minimal or no:
- •
Ground glass
- •
Nodules
- •
Adenopathy
- •
Cysts (other than honeycombing)
- •
- •
- •
Diagnostic workup involves a clinical and/or immunologic screen for other, nonidiopathic causes:
- •
Hypersensitivity and pneumoconiosis
- •
Connective tissue disease
- •
Medications associated with DPLD
- •
Cigarette smoking
- •
- •
Management of definite UIP (CT scan pattern)/IPF (no cause found during workup)
- •
Explain to the patient the disease and the prognosis in understandable terms, hitting the key points:
- •
IPF is a poorly understood disease involving scarring of the lungs
- •
It often progresses in a stepwise fashion (times of stability punctuated by acute exacerbations, without return to previous baseline)
- •
It threatens possible death from respiratory failure over a 3–5-year period
- •
New medications are available that may slow the disease process
- •
Lung transplant may be required
- •
- •
- •
Consider:
- •
Referral to an end-stage lung disease clinic as a part of the lung transplant evaluation process
- •
Starting a proton pump inhibitor (supported by retrospective data)
- •
Starting pirfenidone or nintedanib (choose based on cardiac disease or side effect profile)
- •
Nintedanib has a “black box” warning for ischemic heart disease and is more likely to cause lower-GI side effects
- •
Pirfenidone does not carry a cardiovascular warning and causes upper-GI side effects
- •
Intolerance of both of these medications is relatively common
- •
- •
Ensuring/maintaining euvolemia (ie, no edema) with loop diuretics as necessary
- •
Both left- and isolated right-sided heart failure complicate UIP/IPF, decreasing exercise tolerance
- •
- •
Serial PFTs every 3 months with a clinical screen for symptom progression, superimposed heart failure, and medication intolerance
- •
- •
Management of definite UIP (CT scan pattern) with possible cause found during workup
- •
Treat as possible UIP/NSIP/HP
- •
- •
- •
