Other Interstitial Lung Diseases – Insights in ILD

Other Interstitial Lung Diseases – Insights in ILD

Lymphangioleiomyomatosis – Insights in ILD

Lymphangioleiomyomatosis Disease Definition – Insights in ILD

• Pulmonary vasculitis is characterized by inflammation and necrosis of the vasculature, commonly the capillaries¹
• DAH is the most common manifestation of pulmonary vasculitis. DAH is characterized by the widespread extravasation of red blood cells and collecting in the alveoli^1,2

Lymphangioleiomyomatosis Epidemiology – Insights in ILD

• Highly variable¹
• Patients commonly present with nonspecific symptoms that can develop acutely or over time^1,2
  • Dyspnea
  • Cough
  • Fever
  • Chest pain
• A majority of patients (~67%) experience a variable degree of hemoptysis¹
• Anemia – acute or chronic (lasting several weeks) – is common²

Lymphangioleiomyomatosis Disease Course – Insights in ILD

• Patients will often have signs and symptoms of a related systemic disorder¹
• Patient presentation can range from being asymptomatic with radiographic abnormalities to severe respiratory failure resulting from impaired oxygen uptake from the alveoli^1,2

Lymphangioleiomyomatosis Clinical Presentation – Insights in ILD

• Decreased hemoglobin and/or hematocrit levels without external bleeding in addition to increasing pulmonary alveolar opacities is characteristic of DAH¹
• Identification of the underlying systemic disease causing DAHis crucial²
  • Review of systems including exposure history
  • Past medical history
  • Comprehensive physical exam                                               

Lymphangioleiomyomatosis Diagnosis – Insights in ILD

• Diagnostic gold standard to show alveolar hemorrhage as well as the inflamed capillaries¹
• Histologic confirmation of vascular inflammation is required²

• Nonspecific, varies through disease course^1,2
• Alveolar opacities – focal or diffuse areas of ground glass and/or consolidation^1,2
• Opacities are bilateral, patchy or diffuse, dominant in mid and lower zones ofthe lungs¹
• Pleural effusion is not a feature of DAH  if present, suspect heart or renal failure¹

• Frequently required to accurately diagnose DAH²
• Confirms presence of blood in the alveoli and rules out infection²

• Because of nonspecific presentation, comprehensive panels should be done including CBC, coagulation, serum creatinine, and ANCA testing²

Lymphangioleiomyomatosis Management – Insights in ILD

• Recommendations for management are disease specific once an underlying cause is identified¹
  • Non-immune mediated causes are managed by treating thesystemic disease
  • Immune-mediated cases require immediate administration of high-dose glucocorticoids
• Supportive care including ventilatory support (eg, oxygen supplementation, mechanical ventilation)¹

Pulmonary Langerhans Cell Histiocytosis – Insights in ILD

Pulmonary Langerhans Cell Histiocytosis Disease Definition – Insights in ILD

• Proliferation of monoclonal CD1a-positive Langerhans cells that infiltrate the bronchioles and alveolar interstitium, along with lymphocytes, plasma cells, neutrophils, and eosinophils^1,2

Pulmonary Langerhans Cell Histiocytosis Epidemiology – Insights in ILD

Pulmonary Langerhans Cell Histiocytosis Risk Factors – Insights in ILD

Pulmonary Langerhans Cell Histiocytosis Clinical Presentation – Insights in ILD

• Dyspnea
• Nonproductive cough
• Fatigue
• Fever
• Weight loss
• Pleuritic chest pain

Common Patient Presentations of PLCH – Insights in ILD

Pulmonary Langerhans Cell Histiocytosis Diagnosis – Insights in ILD

• CXR shows bilaterally symmetric nodular opacities in the middle and upper lung fields with cystic changes
• Lung bases are often spared
• Diagnosis is confirmed with an HRCT – can differentiate PLCH from other cystic lung diseases (eg, LAM, emphysema)

• Findings are normal, restrictive, obstructive, or mixed depending on when the test is done during the course of the disease
• Most commonly, the DL_CO is reduced

• Indicated when imaging and PFTs are inconclusive
• Finding >5% of CD1a cells in BAL is highly suggestive of disease

Pulmonary Langerhans Cell Histiocytosis Management – Insights in ILD

• A majority of patients recover or remain stable without treatment¹
• Primary treatment is smoking cessation – with disease resolving in ~33% of patients²
• Empiric use of corticosteroids and cytotoxic drugs, although efficacy is unproven^1,2
• Lung transplantation is curative when combined with smoking cessation²

Exposure Related Interstitial Lung Disease – Insights in ILD

Exposure-Related Interstitial Lung Disease Overview – Insights in ILD

• Unknown etiology characterized by rapid eosinophilic infiltration of the lung interstitium
• Can be caused by tobacco exposure, medications, fungal/parasitic infection

• Acute or subacute illness that recurs
• May be allergy related

Drug-Associated Interstitial Lung Disease – Insights in ILD

• Often affects otherwise healthy patients, usually smokers, men age 20-40

• Most patients are nonsmokers
• Patients may have allergy or asthma history

Drug-Associated Interstitial Lung Disease Overview – Insights in ILD

• Nonproductive cough
• Dyspnea
• Malaise
• Myalgias
• Night sweats
• Pleuritic chest pain
• Tachypnea
• Fever (>38.5°C)
• Bibasilar inspiratory crackles
• Rhonchi on forced exhalation

• Cough
• Fever
• Progressive dyspnea
• Wheezing
• Night sweats
• Weight loss if symptoms are recurrent

Drug-Associated ILD Causative Agents – Insights in ILD

• Bilateral, random, patchy ground-glass or reticular opacities, consolidation opacities, and smooth interlobular septal thickening
• Small, bilateral, pleural effusions occur in ~67% of patients

• Fails to demonstrate significantly elevated eosinophil counts
• ESR and IgE levels are high but nonspecific

• Marked eosinophilia with high pH

• Restrictive process with reduced DL_CO

• BAL shows high number and percentage (>25%) of eosinophils
• Biopsy shows eosinophilic infiltration with acute and organizing diffuse alveolar damage – rarely needed

• Bilateral peripheral or pleural-based opacities, most commonly in the middle and upper lung zones

• Peripheral blood eosinophilia, high ESR, iron deficiency anemia, and thrombocytosis are present

• Usually done to confirm the diagnosis
• Eosinophilia >40% is highly suggestive of CEP

Drug-Associated ILD Epidemiology – Insights in ILD

1. Acute respiratory illness (duration <1 month)
2. Pulmonary infiltrates on imaging
3. Pulmonary eosinophilia (>25% eosinophils in BAL fluid) or eosinophilic pneumonia on lung biopsy
4. Absence of other specific pulmonary eosinophilic diseases

Drug-Associated ILD Symptoms – Insights in ILD

1. Respiratory symptoms (duration > 2 weeks)
2. Alveolar and/or blood eosinophilia
3. Peripheral pulmonary infiltrates on imaging
4. Exclusion of any known causes

Drug-Associated ILD Clinical Presentation – Insights in ILD

• Systemic corticosteroids; if applicable, remove identified trigger or exposure
• Prognosis is usually good
• Patients commonly respond to corticosteroids with full recovery
• Resolution of symptoms within 24-48h, radiographic abnormalities within 30 d

• Systemic corticosteroids
• Maintenance therapy: inhaled corticosteroids, oral corticosteroids, or both
• Failure to respond (within 48h) to steroids suggests another diagnosis
• Resolution of symptoms and radiographic abnormalities in 14-30 d

Drug-Associated ILD Pathogenesis – Insights in ILD

Drug-Associated ILD Disease Progression – Insights in ILD

• 3 major forms: type 1 (NF1), type 2 (NF2), schwannomatosis^1,2
• NF1 (von Recklinghausen disease) is the most common type and also exhibits thoracic manifestations³

Drug-Associated Interstitial Lung Disease Diagnosis – Insights in ILD

• NF1 is an autosomal dominant genetic disorder with an incidence of approximately 1 in 2600 to 3000 individuals^1,2
• Approximately 5% of NF1 patients develop mediastinal tumors³
• A total of 64 cases of NF-associated diffuse lung disease have been identified⁴

Drug-Associated Interstitial Lung Disease Diagnosis (Continued) –Insights in ILD

1. Presence of ≥6 café au lait macules, >5mm in diameter pre-puberty or ≥1.5mm post-puberty
2. Skin-fold freckling
3. ≥2 neurofibromas or 1 plexiform neurofibroma
4. ≥2 iris hamartomas (Lisch nodules)
5. Optic glioma
6. Skeletal dysplasia
7. Affected first-degree relative

Drug-Associated Interstitial Lung Disease Risk Factors – Insights in ILD

Drug-Associated ILD Risk Factors of Children and Elderly – Insights in ILD

• Neurofibroma: well-circumscribed round or elliptic masses in the paravertebral regions or along the nerves’ courses
  • May erode, invade, or destroy adjacent bone; may calcify
• Focal thoracic scoliosis
• Posterior vertebral scalloping
• Enlarged neural foramina
• Characteristic rib abnormalities – due to bone dysplasia or erosion from adjacent neurofibromas

Drug-Associated ILD Risk Factors of Gender – Insights in ILD

• Lung Parenchymal Disease¹
  • Cysts and bullae formation: upper lobe
  • Diffuse interstitial fibrosis: lower lobe
    • Ground-glass opacification
    • Basilar reticular abnormalities
• Secondary Pulmonary Arterial Hypertension²

Drug-Associated ILD Risk Factors of Reactive Oxygen Species – Insights in ILD

• Aims at early detection and symptomatic treatment of complications as they occur
• The decision to obtain testing such as imaging studies depends on the history and physical findings
• There is no overall treatment for NF1 or any therapeutic agents specifically approved for patients with NF1

Drug-Associated ILD Risk Factors of Drug Interactions – Insights in ILD

Drug-Associated Interstitial Lung Disease Management – Insights in ILD

• Characterized by proliferation of atypical smooth muscle cells throughout the chest leading to destruction and infiltration of the lung parenchyma, cystic emphysema, and progressive deterioration of lung function^1-3
• Low-grade, destructive, metastasizing neoplasm that spreads through the lymphatic system¹

Occupational Interstitial Lung Disease – Insights in ILD

• Rare, affects <1 in 1 million people^1,2
• Occurs exclusively in women aged 20-40^1,2
• Prognosis is uncertain because clinical course is variable^2,3
  • Median survival is likely >8y from diagnosis
  • Progression may accelerate during pregnancy

The Pneumoconioses of Interstitial Lung Disease – Insights in ILD

• Slowly progressive and over years often leads to respiratory failure and death
• Lung function declines 2-3x faster than a healthy person
• NOT an ILD

Pneumoconioses Epidemiology and Mortality – Insights in ILD

• Dyspnea
• Cough
• Chest pain
• Hemoptysis
• Spontaneous pneumothorax is common (36%)

Pneumoconioses Presenting Symptoms – Insights in ILD

• Multiple, small, diffusely distributed cysts

• If HRCT is nondiagnostic
• Abnormal proliferation of LAM cells with cystic changes

• Obstructive or mixed obstructive and restrictive pattern
• Increased TLC and RV
• Reduced PaO₂ and DL_CO

Pneumoconioses Disease Progression – Insights in ILD

• mTOR inhibitors can stabilize or slow decline in pulmonary function in patients who have progressive disease, with FEV₁ <70%
• Lung transplantation

Common Disease Manifestations in Occupations – Insights in ILD

Clinical Presentation and Diagnostic Considerations in Occupational ILDs– Insights in ILD

Pneumoconiosis Diagnosis – Insights in ILD

Pneumoconiosis Diagnostic Tests – Insights in ILD

Pneumoconiosis Diagnostic Tests (Continued) – Insights in ILD

Pneumoconiosis Risk Factors – Insights in ILD

Pneumoconiosis Disease and Symptom Management – Insights in ILD

Asbestosis Pneumoconiosis – Insights in ILD

Silicosis Pneumoconiosis – Insights in ILD

Coal Mine Dust Lung Disease Pneumoconiosis – Insights in ILD

Chronic Beryllium Disease Pneumoconiosis – Insights in ILD

Vasculitis/Diffuse Alveolar Hemorrhage – Insights in ILD

Diffuse Alveolar Hemorrhage Disease Definition – Insights in ILD

Diffuse Alveolar Hemorrhage Clinical Presentation – Insights in ILD

Diffuse Alveolar Hemorrhage Clinical Presentation (Continued) – Insights in ILD

Diffuse Alveolar Hemorrhage Diagnosis – Insights in ILD

Diagnosis of Diffuse Alveolar Hemorrhage – Insights in ILD

Management of Diffuse Alveolar Hemorrhage – Insights in ILD

Other Rare Interstitial Lung Diseases – Insights in ILD

Eosinophilic Pneumonia – Insights in ILD

Eosinophilic Pneumonia Disease Definition – Insights in ILD

Eosinophilic Pneumonia Epidemiology and Risk Factors – Insights in ILD

Eosinophilic Pneumonia Clinical Presentation – Insights in ILD

Eosinophilic Pneumonia Diagnostic Tests – Insights in ILD

Diagnosis of AEP – Insights in ILD

Diagnosis of CEP – Insights in ILD

Disease Management of AEP and CEP – Insights in ILD

Neurofibromatosis – Insights in ILD

Neurofibromatosis Disease Definition – Insights in ILD

Neurofibromatosis Epidemiology – Insights in ILD

Diagnosis of NF1 – Insights in ILD

Clinical Presentation of NF-DLD – Insights in ILD

Thoracic Manifestations – Insights in ILD

Thoracic Manifestations (Continued) – Insights in ILD

Management – Insights in ILD