Diffuse Parenchymal (Interstitial) Lung Diseases
Diffuse parenchymal (interstitial) lung disease (DPLD/ILD) describes a group of disorders characterized by inflammatio and/or fibrosi of the pulmonary interstitium (i.e. tissue between the alveolar epithelium and capillary endothelium) and the bronchovascular and septal tissues, comprising the lung's f brous framework. Alveolar airspaces, distal airways and vasculature may also be involved.
Clinical features: Insidious onset of dyspnoea and cough, bilateral inspiratory crackles ( ± clubbing) and exercise-induced desaturation are common to all DPLD. Hypoxaemia and right-sided heart failure occur in advanced disease. Pulmonary function tests (PFT) reveal a restrictive defect with reduced total lung capacity (TLC), functional residual capacity (FRC) and residual volume (RV) due to impaired lung compliance. Gas transfer (DLco) is decreased due to diminished surface area for gas exchange. Chest X-ray (CXR) is abnormal (>90%) with mainly lower lobe alveolar, interstitial or mixed infiltrates Bronchoalveolar lavage (BAL) excludes other diseases (e.g. malignancy). An increase in BAL inflammator cells indicates alveolitis and corre- lates with ground glass opacificatio (GGO) on high resolution computed tomography (HRCT) scans and may reflec rapidly progressive or potentially reversible disease. HRCT scans ( ± histology) are required classification
Classiﬁcation: There are four main categories of DPLD (Fig. 30a) with considerable overlap:
1 Idiopathic interstitial pneumonitis (IIP) has two subgroups:
· Usual interstitial pneumonia (UIP; previously known as idiopathic pulmonary fibrosi (IPF) or cryptogenic f brosing alveolitis), causes approximately 70% of IIP. Pathogenesis involves minimal inflammatio with fibrosi due to fibroblas proliferation and abnormal alveolar epithelial healing. Incidence is approximately 5/105/year. It usually occurs in older men, aged approximately 70 years. Clinical features include progressive dyspnoea, cough, clubbing (25-50%) and basal inspiratory crepitations interspersed with acute 'exacerbations'. HRCT scans show bilateral, basal and subpleural reticular changes with honeycombing and/or traction bronchiectasis (Fig. 30d). Consolidation, GGO and nodules are infrequent. Histology reveals peripheral, patchy damage, f brosis and honeycombing alternating with areas of normal lung. A similar picture occurs in asbestosis, collagen vascular and drug-induced diseases. Diffuse alveolar damage (DAD) and cryptogenic organizing pneumonia (COP) occur during acute exacerbations. Treatment: UIP does not respond to steroids or immunosuppressants. Median survival from diagnosis is <3 years and worse in smokers.
· Non-usual interstitial pneumonitis (non-UIP) causes approximately 30% of IIP. Differences in clinical course, histology, HRCT and outcome suggest that these rare disorders are distinct clinico- pathologic entities. They include (in order of frequency) non-specifi interstitial pneumonitis (NSIP), COP, previously known as bronchiolitis obliterans organising pneumonia (BOOP), acute interstitial pneumonitis (AIP; formerly known as Hamman-Rich syndrome), respiratory bronchiolitis-interstitial lung disease (RB-ILD), desquamative interstitial pneumonitis (DIP) and lymphoid interstitial pneumonitis (LIP). Clinical and radiological features, treatment response and prognosis are summarized in Fig. 30g. Presentation is earlier, mainly in men, aged 40-50 years. Pulmonary involvement is diffuse, (with subpleural sparing), less f brotic and more cellular (Fig. 30e) than UIP. HRCT scans may show bilateral GGO, which may be widespread, subpleural or basal (Fig. 30f). About 50% of cases are sensitive to steroid ( immunosuppressive) therapy with a median survival of >10 years. However, prognosis may be poor in steroid-resistant disease (e.g. AIP ≤6 months).
2 DPLD due to speciﬁc causes include
· Drug-induced DPLD (Fig. 30b). Mechanisms include oxidantmediated injury (e.g. nitrofurantoin), direct cytotoxic effects (e.g. bleomycin), cellular phospholipid deposition (e.g. amiodarone) and immune-mediated injury (e.g. hydralazine). Treatment includes drug withdrawal and occasionally steroid therapy. Irreversible damage may cause respiratory failure (e.g. amiodarone).
· Hypersensitivity pneumonitis (HP; also known as extrinsic al- lergic alveolitis) is discussed in Chapter 33. It is an inflammator response to inhaled, mainly organic antigens, to which the patient has become sensitized (e.g. thermophilic actinomycetes in mouldy hay).
· Connective tissue disease (CTD) DPLD occurs in 5% of rheumatoid arthritis (RA) patients, especially those with multisystem disease (e.g. vasculitis and nodules) but is usually asymptomatic. Symptomatic DPLD occurs in many other CTD (Fig. 30c) and after some treatments (e.g. methotrexate and gold). NSIP is the predominant histological pattern except in RA, where 50% have a UIP pattern.
· Occupational lung disease follows inhalation of mainly mineral (e.g. coal and asbestos) dusts (Chapter 33).
3 Granulomatous DPLD: sarcoidosis, the second most frequent DPLD, and other granulomatous DPLD are discussed in Chapter 31. 4 Rare causes of DPLD include infiltrat ve (e.g. amyloidosis), ma- lignant (e.g. lymphangitis carcinomatosis), post-inflammator (e.g. ARDS and vasculitis), post-infective (e.g. HIV), bone marrow transplantation and rare lung diseases (e.g. Langerhan's cell histiocytosis).
Diagnosis (Fig. 30a): DPLD due to occupational exposure, drugs, CTD, HP or sarcoidosis is often diagnosed after a comprehensive his- tory (i.e. occupational exposure), careful examination (e.g. for CTD), blood tests (e.g. rheumatoid factor), serology (e.g. avian precipitans), PFT and radiological imaging. In contrast, initial diagnosis of IIP is one of exclusion. Subsequent classification to distinguish UIP from other IIP (e.g. NSIP), has important therapeutic and prognostic implications and requires an integrated clinical, radiological and pathological approach. HRCT scans aid differentiation. Typical clinical and HRCT features allow confiden diagnosis of UIP (sensitivity 43-78%, specificit 90-97%) and avoid the need for biopsy in 50% of cases. Surgical biopsy is considered if radiology is not diagnostic and in non-UIP cases. Transbronchial biopsies are usually inadequate for histological classificatio but may be diagnostic in sarcoidosis.
Treatment is considered in patients with rapidly deteriorating symptoms, inflammator changes (e.g. GGO) or if requested despite poor evidence for benefi (e.g. UTP). Supportive therapy requires supplemental oxygen, pulmonary rehabilitation, nutrition, smoking cessation and palliative care. Pharmacological therapy includes steroids and/or immunosuppressive agents (e.g. azothioprine, methotrexate and cyclophosphamide). Tn steroid-sensitive conditions (e.g. COP, DTP and NSTP), a short trial of high-dose steroids may be indicated. However, in patients requiring ongoing therapy or less likely to respond (e.g. UTP), combination 'triple' therapy with low-dose prednisolone, azothioprine and N-acetylcysteine (NAC) is usually recommended. Tn many patients, therapy is ineffective and has significan side effects. Consider early referral for lung transplantation.