🫀🫁Cardio & Resp🫀🫁 - Restrictive Lung Diseases Flashcards
What is a restrictive lung disease?
A disease that restricts the expansion/volume of the lungs
What are the 2 categories of restrictive lung disease?
Intrinsic lung disease - alterations to lung parenchyma
Extrinsic disorders - compress lungs or limit expansion
What do extrinsic disorders usually effect?
Pleura
Chest wall
Neuromuscular (decrease ability of respiratory muscles to inflate / deflate the lungs)
What is the most significant cause of intrinsic lung disease?
Interstitial lung disease
Outline the cells found in the lung parenchyma
What is found within the interstitial space of the lungs
Interstitial space – space between alveolar epithelium and capillary endothelium.
Contains lymphatic vessels, occasional fibroblasts and ECM
Structural support to lung
Very thin (few micrometers thick) to facilitate gas exchange
What key point must be remembered about macrophages’ relationship with the lungs?
What are the categories of interstitial lung diseases (ILD)?
Idiopathic
Autoimmune-related
Exposure related
With cysts or airspace filling
Sarcoidosis
Others (eosinophilic pneumonia etc…)
Give some examples of idiopathic ILDs
Idiopathic pulmonary fibrosis (IPF)
Nonspecific interstitial pneumonia (NSIP)
Desquamative interstitial pneumonia (DIP)
Give some examples of autoimmune-related ILDs
Connective tissue disease (CTD) associated
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD)
Systemic sclerosis interstitial lung disease (SSc-ILD)
Give some examples of exposure related ILDs
Hypersensitivity pneumonitis (HP)
Drug induced etc…
What is the classic clinical presentation for ILDs?
Progressive breathlessness
Non-productive cough
Limitation in exercise tolerance
(Symptoms of CTD)
Can be useful:
-Occupational and exposure history
-Medication history (drug induced ILD)
-Family history (strong familial connections with idiopathic ILDs)
What would be found upon clinical examination of a patient with ILD?
Low oxygen saturations (resting or exertion)
Fine bilateral inspiratory crackles
Digital clubbing
(+/- features of CTD - skin, joints, muscles)
What are the changes to the lung physiology in ILD?
Scarring makes lungs stiff - decrease in lung compliance
↓ Lung volumes (TLC, FRC, RV)
↓ FVC
↓ diffusing capacity of lung for carbon monoxide (DLCO)
↓ arterial PO2 – particularly with exercise
FEV1/ FVC ratio stays normal (sometimes even elevated)
What investigation is used for ILD diagnosis?
High-resolution CT (HRCT)
Rotating X-ray images to generate cross-sectional images
High - density substances e.g. bone absorb more x-rays and appear whiter
Low - density substances e.g. air absorb few x-rays and appear darker
Same as a standard X-ray
What is usual interstitial pneumonia (UIP)?
Usual interstitial pneumonia (UIP) is a histologic pattern
Strongly associated with ILDs, such as IPF
What would you see in a HRCT of usual interstitial pneumonia (UIP)?
Honeycombing - Clustered cystic spaces with well-defined walls
Traction bronchiectasis due to fibrosis pulling on bronchi
Minimal or absent ground-glass opacity
Commonly associated with IPF
Predominantly in the posterior and basal lungs
What would you see in a HRCT of NSIP?
Predominant ground-glass opacities
Some honeycombing, but much less than UIP
Involves the bilateral lower lobes but more uniform and diffuse than UIP
What would you see in organising pneumonia?
Patchy, consolidation-like opacities, often subpleural or around bronchioles
No honeycombing or significant reticulation
Seen in cryptogenic organising pneumonia (COP) or secondary to infections, drugs, or autoimmune conditions
What are the general principles of ILD management for early disease?
Pharmacological therapy – immunosuppressive drugs, antifibrotics
Clinical trials
Patient education
Vaccination
Smoking cessation
Treatment of co-morbidities – gastroesophageal reflux, obstructive sleep apnoea, pulmonary hypertension
Pulmonary rehabilitation
What are the principles of late stage ILD treatment?
Supplemental oxygen
Lung transplantation
Palliative care - symptom management, end-of-life care
What is idiopathic pulmonary fibrosis (IPF)?
Progressive, scarring lung disease of unknown cause
1% of all deaths in the UK
Average decline in FVC
Summarise the clinical trajectory of IPF
Highly variable
Feature progressive decline, but also sudden extreme decline due to acute exacerbations possible
What is the prognosis of IPF?
Poor
Mediant untreated survival 3-5years
What are the predisposing factors for IPF?
Genetic susceptibility (MUC5B, DSP)
Environmental triggers (smoking, viruses, pollutants, dusts)
Cellular ageing (telomere attrition, senescence)
What is the proposed mechanism for IPF?
Initial alveolar epithelial injury in the presence of an altered microbiome
Inflammatory response - profibrotic macrophages activated by injury - release fibrosis-promoting cytokines
Fibroblast activation - production of excess ECM, including collagen
Leads to remodelling and honeycomb cyst formation
What do we know for sure about the initiation of IPF?
IPF is initiated by alveolar epithelial injury
What are the key histopathological features of IPF?
Microscopic Honeycomb Cysts (Image b):
-Represents areas of advanced fibrosis with dilated, thick-walled airspaces.
-These cysts are a hallmark of chronic, irreversible lung damage in UIP.
Fibroblastic Foci (Image c):
-Clusters of proliferating fibroblasts and myofibroblasts, often found at the interface between normal lung tissue and fibrotic areas
-Indicate active fibrosis
What is meant by spatial and temporal heterogeneity, in the context of IPF?
Spatial heterogeneity - alternating areas of normal lung tissue, active fibrosis, and honeycombing
Temporal heterogeneity - presence of both early fibrotic lesions (fibroblastic foci) and advanced fibrosis (honeycomb changes) in the same lung biopsy
What is the effectiveness of immunosuppression in IPF?
HARMFUL effect
How is IPF treated?
Antifibrotics
Treatment - no cure
What is hypersensitivity pneumonitis (HP)?
ILD caused by immune-mediated response in susceptible and sensitised individuals - inhaled environmental antigens
Involves small airways and parenchyma
What are the classifications of HP?
Acute HP - Intermittent, high-level exposure – abrupt symptom onset, flu-like syndrome 4-12 hrs after exposure
Chronic HP - Long-term, low-level exposure
-Nonfibrotic (purely inflammatory)
-Fibrotic – associated with higher mortality
What is the epidemiology of HP?
(Rare - incidence in UK ~ 1 per 100,0001
Mean age onset 50 – 60 yrs
M = F
Less frequent in smokers
Worldwide prevalence varies due to differences in antigen exposure, agricultural, industrial practices etc.
3- fold ↑ risk of death compared to general population)
What is the driving force behind HP?
Immunological dysregulation
Antigen exposure and processing by the innate immune system
Inflammatory response mediated by T-helper cells and antigen-specific IgG antibodies
Accumulation of lymphocytes and formation of granulomas
How is HP diagnosed?
Detailed exposure history – antigen not identified in approx. 50% of cases
Inspiratory ‘squeaks’ on auscultation - caused by the coexisting bronchiolitis
Specific circulating IgG antibodies (serum precipitins) to potential antigens
HRCT imaging
Bronchoalveolar lavage (BAL) - lymphocyte count >30% indicative of HP
What would you expect to see in an HRCT of HP?
Bronchiolocentric inflammation (centrilobular ground-glass nodules)
Narrowing of small airways (air trapping)
Interstitial inflammation (ground-glass opacity)
Mosaic attenuation and three-density patterns
What is the treatment for HP?
Complete antigen removal / avoidance is crucial
Corticosteroids often used
Immunosuppressants e.g. mycophenolate mofetil (MMF) and azathioprine used but poor evidence base
Progressive, fibrotic HP – Nintedanib (antifibrotic)
What is SSc-ILD?
Systemic sclerosis associated ILD
Autoimmune connective tissue disease characterised by immune dysregulation and progressive fibrosis that affects skin, with variable internal organ involvement
Rare - 10 – 50 cases per 1,000,000 per year
ILD develops in 30-40 % and is most common cause of death – 10-year mortality of 40%
What are the clinical features of SSc?
Classified based on skin involvement -
Limited cutaneous SSc
(Pulmonary hypertension more common)
OR
Diffuse cutaneous SSc
(ILD more common)
What is the pathogenesis of SSc-ILD?
Endothelial injury - increased permeability and recruitment of inflammatory cells into lung tissue
Autoimmunity and Inflammation - activation of T cells, B cells, and macrophages - overproduction of autoantibodies and cytokines
Fibroblast activation - excessive ECM deposition
Leads to progressive fibrosis
What is the difference between SSc-ILD and IPF?
SSc-ILD secondary to systemic sclerosis, IPF cause is unknown
SSc-ILD has major inflammatory factor, which IPF does not
SSc-ILD characterised by non-specific interstitial pneumonia (NSIP), IPF features usual interstitial pneumonia (UIP)
What are the management options for SSc-ILD?
Determined by disease extent on HRCT and lung function trajectory (monitor every 3 – 6 months)
Corticosteroid use is controversial and risk of renal crisis with high doses (>10mg/day)
Immunosuppressives – cyclophosphamide, mycophenolate mofetil
Progressive fibrotic phenotype– Nintedanib (antifibrotic)
