Lecture 21:ILD 2 Flashcards
what are the Interstitial lung diseases?
- -Heterogeneous group of diseases
- -Confusing and duplication of disease names
- -Poor classification
- -Fibrotic lung disease
- -Restrictive defect on pulmonary function
- -Diagnostically & therapeutically challenging
what is the definition of ILDs?
group of disorders that result in disruption of the distal lung parenchyma
what is the interstitium?
alveolar walls and septae and contains the lung connective tissue elements
what is the hallmark of ILDs?
- -FIBROSIS
- -An extensive alteration of alveolar/airway architecture
What is Pulmonary Fibrosis?
- -Pulmonary Fibrosis = scarring of the lung.
- -Gradually, the alveoli become replaced by fibrotic tissue.
- -When the scar forms, the tissue becomes thicker causing a loss of the tissue’s ability to transfer oxygen into the bloodstream.
classification of ILDs?
1) Aetiological
2) Radiological: most used clinically
2) Histological: (if tissue specimen available)
- -In general the more cellular the picture, the more treatment responsive;
- -Treatment is typically steroids or other immunosuppression
etiological classification of ILDs?
1)Idiopathic:
–Idiopathic pulmonary fibrosis, sarcoidosis, Langerhans cell histiocytosis
2)Collagen vascular disease associated:
–Systemic disease e.g. scleroderma, rheumatoid arthritis
3)Drug/treatment-related:
–E.g. amiodarone, nitrofurantoin, bleomycin, MTX, radiation
4)Occupational or environmental exposures:
–Inorganic: e.g. asbestosis, silicosis.
–Organic dust: (hypersensitivity pneumonitis)
pigeon-fanciers, farmers lung, etc
5)Post-infectious: e.g. TB
radiological classification of ILDs?
- -Based on zones most affected on CX
- -Upper zones
- -Lower zones
Upper versus Lower zone fibrosis?
1)CHHARTS (top of the charts = Upper lobe)
Coalworkers, Hypersensitivity, Histiocytosis X, –Ankylosing spondylitis, Radiation, Tuberculosis, Silicosis
2)RAIDS (for lower lobe)
–Rheumatoid arthritis, Asbestosis, IPF, Drugs, Scleroderma,
histological classification of ILDs?
- -Usual interstitial pneumonitis (UIP)
- -Non-specific interstitial pneumonitis (NSIP)
- -Desquamitive interstitial pneumonitis (DIP)
- -Respiratory Bronchiolitis interstitial lung disease (RB-ILD)
- -Lymphocytic interstitial pneumonitis (LIP)
- -Acute interstitial pneumonia (AIP)
- -Bronchiolitis obliterans organizing pneumonia (BOOP)
list drugs causing pulmonary fibrosis
amiodarone, nitrofurantoin, bleomycin, MTX, radiation
Rheumatoid arthritis, Asbestosis, IPF, Drugs, Scleroderma predominantly affect upper lobes. T/F
False
1)CHHARTS (top of the charts = Upper lobe)
Coalworkers, Hypersensitivity, Histiocytosis X, –Ankylosing spondylitis, Radiation, Tuberculosis, Silicosis
2)RAIDS (for lower lobe)
–Rheumatoid arthritis, Asbestosis, IPF, Drugs, Scleroderma,
what is the bronchiolitis obliterans?
A chronic disease of the small airways, usually caused by repeated cycles of inflammation and scarring. Over time, scarring builds up and causes obstructive lung disease. Common etiologies include inhalation of toxic fumes and severe adenovirus pneumonia.
in history taking of patients with ILD, what are the most likely findings to be discovered?
1) progressive exertional dyspnoea
2) Gradual history 6-12 months or more
3) ± Dry cough - Productive cough is rare for interstitial lung disease
* * No wheeze
4) Occasionally there may be chest findings and impressive radiology findings with minimal SOB e.g. 5)Sarcoidosis
6) Haemoptysis unusual
7) New hemoptysis in old ILD; consider malignancy
why wheeze is not seen in ILDs?
because wheezing is a sign of obstructive diseases, whereas ILDs are restrictive.
does hemoptysis is common finding in ILD?
- -no,
- -New hemoptysis in old ILD; consider malignancy
list some history clues suggesting ILD.
1) Age:
- -Most Idiopathic Pulmonary Fibrosis patients are >60 years old at presentation
- -Most Sarcoidosis and Connective Tissue associated ILD present between 20-40 years old
2) Smoking:
- -Idiopathic Pulmonary Fibrosis (IPF)
- -Respiratory bronchiolitis-ILD
3) Gender: Connective Tissue associated ILD is commoner in women
- -Duration: acute/subacute Interstitial lung disease(ILD) often confused with pneumonia
4) Meds: include OTC meds, protein supplements, and remote drug hx (e.g. amiodarone)
smoking is a risk factor for IPF. T/F
True
Risk factors: cigarette smoking, environmental or occupational exposures, chronic aspiration, genetic predisposition
connective tissue disorder associated ILDsare more common in males. T/F
False
Connective Tissue associated ILD is commoner in women
what occupations predispose to ILDs?
- -sand blasting (silica), coal miners
- -asbestos
- -hay farming, mushroom farming – hypersensitivity pneumonitis (HP) (symptoms may lessen if away for a week and return upon re-exposure).
- -Hobbies – pigeon fancier (HSP)
what are the typical signs of symptoms of CTDs that can be acquired during history taking?
- -Musculoskeletal pain, weakness, fatigue, fever, joint pain or swelling, photosensitivity, pleuritis, dry eyes/mouth
- -Scleroderma symptoms – tightening of the skin over hands, mouth, nose. Raynaud’s phenomenon, swallowing difficulties.
what are the possible signs on P/E of a patient with ILD?
- -General summary of signs:
- -Abnormal but non-specific
1) Digital Clubbing: common in IPF, asbestosis. Rare in sarcoidosis
2) Crackles (“velcro”) common in all ILD - -May occur even with normal CXR
3) Cor pulmonale: due to pulmonary hypertension (loud P2, parasternal heave, elevated JVP if TR).
digital clubbing is common in sarcoidosis. T/F
False
It is common in asbestosis
can crackles be heard in a patient with ILD and normal CXR?
Yes
what are the P/E signs on hands that can suggest ILD or its predisposing disease?
- -Clubbing (IPF & asbestosis)
- -Sclerodactaly (Scleroderma)
- -Vasculitic phenomena: splinter hemorrhages (RA, SLE)
- -Raynaud’s phenomenon (Scleroderma, SLE)
- -Symmetrical small joint arthropathy, onycholysis (RA)
- -Gottren’s papules (Dermatomyositis)
what are the Gottron’s papules?
Erythematous papules on the extensor surfaces of the hands, typically over the metacarpophalangeal (MCP) and interphalangeal joints. A characteristic dermatological finding in dermatomyositis.
what are the P/E signs on the head and neck that can suggest ILD or its predisposing disease?
- -Butterfly rash: SLE
- -Lupus pernio, parotid swelling, LMN VII palsies, iritis: sarcoidosis
- -Keratoconjunctivitis sicca: Sarcoidosis, RA
- -Uveitis: painful red eye, irregular pupil
- -Telangiectasia, microstomia, ‘beaking’ of the nose: Scleroderma
what is the lupus pernio?
An extrapulmonary manifestation of sarcoidosis that most commonly manifests with erythematous to violaceous, indurated lesions on the central face.
what are the P/E signs on the chest that can suggest ILD or its predisposing disease?
1) Rapid shallow breathing
2) ± Central cyanosis
3) ± Tracheal deviation (TB)
4) decreased chest diameter and chest expansion
5) Tactile fremitus: normal or increased
6) Percussion: normal or dull
7) Auscultation: bilateral fine end-inspiratory crepitations/crackles (velcro type)
what happens to tactile fremitus in ILDs?
normal or increased
what is heard on auscultation of patients with ILD?
bilateral fine end-inspiratory crepitations/crackles (velcro type)
some extra-pulmonary manifestations may narrow the differential. Examples?
- -Legs: Erythema Nodosum (Sarcoidosis)
- -Myopathy, small joint arthritis: Mixed connective tissue disease
- -External radiation therapy: post-mastectomy or mediastinal lymphoma – Radiation Pneumonitis
what investigations should be performed in suspected ILD?
- -Radiology: Chest X-ray, High Res CT thorax (HRCT)
- -Pulmonary Function Testing (PFT)
- -Blood tests
- -Functional assessments: Arterial Blood Gas, 6 Min Walk Test, ± Echocardiogram
- -(±) Bronchoscopy
- -(±) Tissue sampling/biopsy (Histology)
what are the characteristic CXR findings of a patient with ILD?
- -Bilateral interstitial infiltrates
- -Can be patchy or nodular
- -May occasionally be asymmetrical
- -Starts peripherally
- -No other signs of CCF (prominent hilar vessels, upper lobe diversion, small pleural effusions, cardiomegaly)
- -CXR findings are often suggestive of Interstitial Lung Disease but seldom pathognomonic
- -Review all previous films
- -Up to 10% have normal CXR
which one is the Gold standard investigative procedure of ILDs?
High Res CT Thorax
- -Coarse reticular (linear) opacities
- -Patchy ground-glass opacities
- -Honeycomb cysts
- -Traction bronchiectasis
- -Prone sections
what are the patterns of fibrosis on HRCT of a patient with ILD
- -IPF; subpleural, lower lobe predominance, associated honeycombing & traction bronchiectasis
- -Peripheral: asbestosis, COP, Connective tissue disease
- -Central (bronchovascular thickening) in sarcoid
what ILDs cause predominantly peripheral fibrosis?
asbestosis, COP, Connective tissue disease
sarcoidosis cause central or peripheral fibrosis?
central
what are the characteristic PFT findings of a patient with ILD?
1)Spirometry
–Restrictive pattern **
–decreasedFEV1, and FVC, but FEV1/FVC > 80%
2)Diffusion Lung Capacity (Transfer factor)
–decreased DLCO – is an indication of alveolar disease
Also get decreased DLCO in anemia, emphysema
3)Lung Volumes
– decreased TLC (Total lung capacity) i.e. small lungs
in ILDs, FEV1/FVC <80. T/F
False
FEV1/FVC > 80%: restrictive pattern
what is the DLCO?
A measure of the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries. Used to identify the cause of hypoxemia or dyspnea and monitor the progression of respiratory diseases.
in what conditions DLCO decrease?
Late interstitial lung disease
- -Post-pneumonectomy
- -Pulmonary edema (e.g., as a result of severe congestive heart failure)
- -Emphysema
- -Pulmonary vascular diseases (pulmonary hypertension, pulmonary embolism, hepatopulmonary syndrome)
- -Early interstitial lung disease
- -Pre-existing carboxyhemoglobinemia (e.g., due to smoking)
- -Anemia
list conditions in which DLCO increases…
- -Obesity
- -Bronchial asthma(severe, due to increased blood flow to alveoli)
- -Polycythemia
- -Mild heart failure and left-to-right cardiac shunts (Due to increased pulmonary capillary volume)
obstructive PFT + ILD suggests?
1) Interstitial lung disease = restrictive ventilatory defect usually
- -FEV1/FVC ratio is preserved or increased (>/= 70%)
2) Obstructive ventilatory defect + ILD suggests
- -COPD+ILD,
- -Sarcoidosis
what should be looked for on the blood of a patient with ILD?
- -, U+E, Liver+Bone profile inc Ca2+ (hypercalcemia in sarcoidosis)
- -ESR, CRP, Rheumatoid factor, ANA, dsDNA, anti-SCL 70, anti-centromere, ANCA, anti-GBM
- -ACE level (not really measured anymore): sarcoidosis
- -Myositis panel
does bronchoscopy is always performed in suspected ILD?
- -Not always necessary (Indication depends on underlying disease suspected e.g. Sarcoidosis)
- -Mediastinal lymph node aspirate (EBUS-TBNA) is often performed to diagnose Sarcoidosis
- -Endobronchial or Transbronchial biopsies for sarcoidosis (superceeded by EBUS-TBNA)
when lung biopsy is indicated in ILDs?
- -Video Assisted Thoracoscopic Surgery (VATS)
- -Not performed anymore if confident of radiological diagnosis of IPF (approx. 10% sent for biopsy)
- -Only recommended if atypical radiological appearance, progressive or unusual clinical features (fever, weight loss, haemoptysis, vasculitis)
what is the idiopathic pulmonary fibrosis?
- -Flagship of ILD/Fibrotic lung disease (i.e. This is the condition most people think of when referring to pulmonary fibrosis)
- -Average age >60’s
- -Slight male preponderance
- -SOB on exertion (6-12 months)
- -Clubbing (80%)
- -Fine end-inspiratory crepitations bibasally
- -Poor prognosis
IPF is commonly seen in young.T/F
False
Average age >60’s
what is the pathophysiology of IPF?
- -Pathogenesis theories:
1) Disease of aging lungs (very long telomeres)
2) Basement membrane damage
3) Oxidative stress
how much is the median survival after dx of IPF?
3 years
what is the treatment of IPF?
1) No effective cure for IPF.
2) PPI (reflux may contribute)
3) Approved anti-fibrotic tx:
- -Pirfenidone
- -Nintedanib (kinase inhibitor)
4) Steroids have been tried, do not respond in true IPF
- -Currently, steroids are not recommended unless there is a suspicion of NSIP.
- -Beware steroid side effects.
5) Oxygen therapy, pulmonary rehab
6) Consider lung transplant referral early if <65years old
7) Consider early palliative measures
list 2 anti-fibrotic medications
- -Pirfenidone
- -Nintedanib (kinase inhibitor)
steroids are recommended in IPF. T/F
False
Steroids have been tried, do not respond in true IPF
–Currently, steroids are not recommended unless there is a suspicion of NSIP.
what is the sarcoidosis?
- -Systemic granulomatous disease of unknown etiology
- -Involves lungs in 90-95% of patients
- -60-80% will remit spontaneously
- -Other organs commonly involved
- -Responds to immunosuppressive therapy
60-80% of patients with sarcoidosis will remit spontaneously. T/F
True
what are the most common signs and symptoms of sarcoidosis?
- -Fever/fatigue, weight loss, malaise: 30%
- -Asymptomatic bi-hilar adenopathy (BHL) or other CXR: 25%
- -BHL + Erythema Nodosum = Lofgren’s syndrome (good prognosis)
- -Pulmonary symptoms: 30-50%
- -Pulmonary involvement (including lymphadenopathy >90%
what is the Lofgren’ssyndrome?
An acute presentation of sarcoidosis that manifests with fever, migratory polyarthritis, erythema nodosum, and bilateral hilar lymphadenopathy.
steroids are recommended in sarcoidosis. T/F
True
- -Hypercalcaemia, Serum ACE
- -Uveitis, keratoconjunctivitis sicca
- -Lupus pernio
- -Hepatic granulomas
- -Generally steroid-responsive
- -Majority of cases (Ireland) do not require treatment
what CMP findings are characteristic of sarcoidosis?
Hypercalcaemia, Serum ACE
what are the extra-pulmonary manifestations of sarcoidosis?
1) Common
- -Peripheral lymph nodes are the most frequent site of extrapulmonary manifestation (40%).
- -Eyes (25%): granulomatous uveitis; blurred vision (ocular sarcoidosis)
- -Skin (25%)
* Lupus pernio: pathognomonic, extensive, purple skin lesions (violaceous skin plaques) on the nose, cheeks, chin, and/or ears; also referred to as epithelioid granulomas of the dermis
* Scar sarcoidosis: inflamed, purple skin infiltration and elevation of old scars or tattoos
2) Other manifestations
- -Musculoskeletal ; bone lesions
- -The nervous system (neurosarcoidosis): cranial nerve palsy (7th cranial nerve palsy is the most common), diabetes insipidus, meningitis, hypopituitarism
- -Heart
- -Liver
- -Kidneys
- -Spleen
what investigations should be performed in suspected sarcoidosis?
- -History & exam
- -CXR +/- High Res CT thorax
- -PFTs
- -Renal/Liver/Bone profile esp. Calcium
- -Urinary calcium, ECG, an Eye exam
- -Tuberculin skin test
- -Histology (non-caseating granulomas)
what other causes of granulomatous inflammation should be excluded to diagnose sarcoidosis?
- -Infections: (TB, fungal): Mantoux, Cultures
- -Foreign Body: IVDU
- -Occupational: Silicosis/Beryllium
- -Hypersensitivity Pneumonitis: Birds/Hot Tubs
- -CTD/vasculitis: WG/SLE
- -Lymphoma/Carcinoma (Biopsy
Sarcoidosis: Whom to Treat?
1) Critical Organ Involvement
2) Progressive Respiratory Disease(3-6 mth observation)
3) Hypercalcemia
4) Ocular
5) Cardiac ** high mortality especially in African American
6) Neurological ** Rare – higher prevalence in Afro-Caribbean
7) Symptoms:
- -Cutaneous
- -Sinonasal (SURT)
- -Systemic illness
- -Joint pain
what is the treatment of sarcoidosis?
1) Isolated pulmonary sarcoidosis: In most cases, no treatment is required. The disease is often asymptomatic, non‑progressive, and has a high rate of spontaneous remission.
2) Symptomatic or extrapulmonary sarcoidosis
- -First line: glucocorticoids
- -Second line: alternative immunosuppressive therapy (e.g., methotrexate or azathioprine), possibly in combination with glucocorticoids
- -Antimalarial drugs (e.g., chloroquine, hydroxychloroquine)
- -Last resort in severe pulmonary disease: lung transplantation
- -NSAIDs are always indicated for symptom relief.
what is the hypersensitivity pneumonitis?
- -Hypersensitivity pneumonitis to organic antigens
- -Thermophilic Actinomycetes, Aspergillus, Avian antigens
- -Farmer’s lung, pigeon fancier’s lung etc
- -Type III and IV hypersensitivity acutely
- -Symptom onset 6-8 hours after exposure
- -Dry cough, SOB, chills, fever (no wheeze)
Basal creps acutely
Does chronic HSP involve upper or lower lung zones?
May progress to chronic disease: type IV hypersensitivity – pulmonary fibrosis (upper zones)
what is the management of HSP?
- -Investigations: serum precipitins, specific IgE
- -Tx: allergen avoidance, air driven mask
- -Steroid responsive (when necessary)
- -Overall good prognosis
how HSP is clinically diagnosed?
- -Exposure to antigen
- -serum precipitins to that antigen
- -Recurrent episodes of symptoms
- -Crackles
- -Increased symptoms after exposure
- -Weight loss
- -98% probability of HP
BAL in HSP is characterized by…
BAL lymphocytosis >30% and HRCT were gold standard one ranomised study of steroids in HP: faster resolution no difference in long term outcome
what is the pneumoconiosis?
- -Alveolitis and fibrosis in response to inorganic dusts
- -occupational
- -Upper zone predominant
- -Coal worker’s lung – progressive massive fibrosis
- -Caplan’s syndrome
- -Silicosis
what are the pulmonary manifestations of RA?
- -Fibrotic lung disease (pattern similar to IPF)
- -Pulmonary nodules
- -Pleuritis
- -Pleural effusion (exudate)
pleural effusion in RA is transudate or exudate?
exudate
what is the radiation pneumonitis?
- -Dose & frequency related (~2500 Rads)
- -Onset ~ 6 months post RTx
- -Area of fibrosis may correspond to RTx mantle
- -May be steroid responsive
list the drugs causing pulmonary fibrosis
- -Bleomycin, Busulphan
- -Methotrexate
- -Nitrofurantoin
- -Amiodarone
- -Prolonged high dose O2
- Any drug can cause an idiosyncratic alveolitis
Other causes of Interstitial Lung Disease
- -Ankylosing spondylitis
- -Progressive systemic sclerosis
- -SLE
- -Wegner’s granulomatosis
- -Churg-Strauss syndrome
- -Polymyositis
- -Dermatomyositis
- -Histiocytosis X
- -Lymphangioleiomyomatosis
- -Chronic eosinophilic pneumonia
- -Eosinophilic granuloma
- -Pulmonary alveolar proteinosis
- -Lymphocytic interstitial pneumonia
what is the eosinophilic granuloma?
A disease caused by clonal proliferation of Langerhans cells (dendritic cells that arise from bone marrow and migrate to skin and lymphoid tissue). Typically occurs in children. Can cause lytic bone lesions, skin rash, fever, hepatosplenomegaly, and lymphadenopathy.
what is the pulmonary alveolar proteinosis?
Pulmonary alveolar proteinosis (PAP) is a rare lung disorder characterized by an abnormal accumulation of surfactant-derived lipoprotein compounds within the alveoli of the lung.
