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Idiopathic Pulmonary Fibrosis
Pathogenesis: - may involve series of nonspecific insults including smoking, infection, chronic aspiration, environmental pollutants, which lead to a form of aberrant wound healing - among the implicated factors are cytokines, abnormal fibroblast activity and collagen metabolism Epidemiology: - prevalence 20/100,000 for males and 13/100,000 for females - presents at age 40-70, mean age at diagnosis 66 years - no distinct geographical or racial distribution - potential risk factors are smoking, environmental exposures (metal dust, wood dust, solvents), viruses (EBV, CMV, influenza, HCV), chronic aspiration (?GERD), drugs (?antidepressants) - familial form, probably autosomal dominant with variable penetrance, is believed to exist Clinical Features: - presents insidiously with gradual onset of dyspnea and a nonproductive, often paroxysmal dry cough; the dyspnea becomes progressive and disabling - sleep disturbance is common even in the absence of sleep apnea and other sleep disorder breathing - characteristic physical findings include dry, end-inspiratory “Velcro” crackles, more prominent at the bases, scattered late inspiratory “squeaks,” and clubbing (25-50%) - late findings include cyanosis, loud P2, RV heave, and peripheral edema from cor pulmonale Workup: - Chest X-ray typically shows diffuse bilateral opacities, worse at bases, often in reticular, nodular, or mixed pattern without significant lymphadenopathy; lung volumes are often reduced - PFT’s show restrictive pattern – volumes are low (TLC, VC, FRC), may be closer to normal in smokers; spirometry shows decreased FEV1 and FVC, but a preserved or increased ratio FEV1/FVC; DLCO is reduced because of mismatch - ABG reveals hypoxemia which may need to be induced by exercise or sleep; CO2 retention signifies endstage disease; exercise testing with serial measurement can be useful - HRCT is up to 90% accurate when a confident diagnosis can be made (which is in 66% of cases); will show patchy, heterogeneous findings including areas of normal parenchyma, ground glass opacity representing interstitial inflammation with alveolitis (should be <30%), and fibrotic, cystic areas of “honeycombing” - to establish diagnosis of an idiopathic interstitial pneumonia, must exclude collagen vascular disease and other causes – scleroderma, RA, SLE, sarcoidosis, HIV, infection - see other handout for classification of idiopathic interstitial pneumonias and where IPF/UIP fit in Bronchoscopy and Lung Biopsy: - BAL is of very limited diagnostic value and is typically useful chiefly to rule out numerous infectious causes; % lymphs in fluid can be of prognostic significance - Transbronchial biopsy is good for some other disorders (sarcoid, Goodpasture’s, infection, tumor), but not for ILD in general because pathology is often patchy and biopsy of fibrosed, cystic areas is both low-yield and risky for pneumothorax - VATS is the preferred method for getting tissue; HRCT is helpful to the surgeons in choosing sites - Biopsies should be from multiple sites, > 2cm, and subpleural, RML, and lingular tissue should be avoided, as they often have nonspecific fibrosis Pathology: - Usual interstitial pneumonia is the “usual” finding – the hallmark is heterogeneous, “variegated” appearance with alternation between normal lung, interstitial inflammation, fibrosis, and honeycombed cystic areas
greater proportion of “inflammatory” findings on HRCT (ground glass. shorter symptomatic period (< 1 year). need to anticipate possibility of steroidinduced DM.there is not much good data. screening and waiting time are even more discouraging than for other organs because of donor availability. only a minority respond to therapy. poor response to initial therapy Therapy: . failed to show significant change in decline of lung function in a nonrandomized study compared to steroids.progression is the rule with IPF. and it may be critical to prevent further worsening in patients whose pulmonary function is already severely compromised . taper again . prednisolone + IFN revealed improvement in TLC and O2 status after 12 months . and decreased exercise O2 desaturation .recommended initial therapy – prednisone 1. 44:280) .cyclosporine – may have some role as a steroid-sparing agent in those awaiting tx . reticular opacity). female sex. 50mg po qd.PPD should be placed prior to starting corticosteroids. post-op course and immunologic factors. maintain WBC’s > 4K.6mg po qd-bid . and the natural history is typically a relentless downhill course . response takes 3-6 mos .indications of response are decreased symptoms. stomatitis. and most trials are tiny (n=10-20) Corticosteroids: .5-1 mg/kg/day for another 12 wk. CBC’s Q2wks x 12 wks. but disease may be more responsive early. have preexisting obesity. especially with transplant being an option for some. increase in 25mg increments to max 150mg. 2mg/kg/day to max 200mg. infertility. osteoporosis. then re-evaluate. TLC increase by > 25%. as the cough is often the most distressing aspect of the disease to patients .interferon gamma 1b – inhibits fibroblast proliferation and collagen synthesis in animals .single-lung tx currently preferred. more involved surgery. improvement in serial PFT’s (FVC increase.1 RCT of concurrent use with steroids shows possible survival advantage (Thorax 1989.0-1. if patient responds.trial of 18 nonresponders to steroids randomized to prednisolone alone vs. cardiac disease. initial response to steroids .colchicine – may block fibrosis. with one small study. improved CXR.pts need to maintain aggressive po hydration. osteoporosis. O2 requirements may be higher than for COPD pts • Antitussives including codeine should be used aggressively. 5-year post-transplant survival approximates 50-60% • Pulmonary Rehab programs can improve exercise tolerance. hepatotoxicity.azathioprine – roughly same role. and re-evaluate patient.a clinical staging system would be helpful.cyclophosphamide – second-line drug in those worsening despite steroids.penicillamine – improved median survival vs. but far better tolerated at 0. keep WBC’s 4K-7K.5 mg/kg/day for 4 wk. malignancy. risks are cystitis.poor prognostic factors – extent of fibrosis on HRCT (especially honeycombing).therapy is less likely to benefit patients who are older than 70.side effects of F/C/myalgia generally resolve after 3 months Transplantation: . risks are myelosuppression.for progressive deterioration in O2 and functional status despite optimal medical management . DLCO increase by >40%). greater proportion of lymphocytes (20-25%) in BAL fluid. malignancy . DM. myelosuppression.- UIP is a term reserved for truly idiopathic cases in which collagen vascular disease has been ruled out and there is no pathologic evidence of occupational lung disease such as asbestosis Prognostic Factors: . then Qmonth . improve quality of life • Activity should be encouraged. taper to 0. endstage honeycomb lung . neuropsychiatric changes Cytotoxic and Antifibrotic Agents: . historical controls in population of steroid failures .indicators of longer survival – age <50.