Selected Other Types of Idiopathic Interstitial Pneumonia

1. Nonspecific interstitial pneumonia (NSIP): A common presentation includes dyspnea and cough of usually 6 to 7 months’ duration in the sixth decade of life. In contrast to idiopathic pulmonary fibrosis (IPF), NSIP more commonly affects women and never-smokers. Diffuse crackles may be audible. Most patients have a restrictive ventilatory defect on pulmonary function tests. High-resolution computed tomography (HRCT) abnormalities include bilateral ground-glass opacities or irregular reticular opacities with traction bronchiectasis. NSIP can be idiopathic but is often associated with an underlying connective tissue disease, especially scleroderma. Connective tissue disease–related interstitial lung disease (CTD-ILD) is the leading cause of mortality in patients with scleroderma and is often characterized by a progressive decline in lung function.

Treatment: To date, no randomized clinical trial of treatment in idiopathic NSIP has been performed, but typical treatment includes glucocorticoids, with or without additional immunosuppressive agents. In patients with scleroderma-related interstitial lung disease (ILD), a randomized controlled trial demonstrated likely similar efficacy of both mycophenolate mofetil and cyclophosphamide.Evidence 1Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness and imprecision. Tashkin DP, Roth MD, Clements PJ, et al; Sclerodema Lung Study II Investigators. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med. 2016 Sep;4(9):708-719. doi: 10.1016/S2213-2600(16)30152-7. Epub 2016 Jul 25. PubMed PMID: 27469583; PubMed Central PMCID: PMC5014629. Furthermore, a recent randomized controlled trial has also demonstrated the clinical value of the tyrosine kinase inhibitor nintedanib in the management of scleroderma-related ILD.Evidence 2Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness and imprecision. Distler O, Highland KB, Gahlemann M, et al; SENSCIS Trial Investigators. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med. 2019 Jun 27;380(26):2518-2528. doi: 10.1056/NEJMoa1903076. Epub 2019 May 20. PubMed PMID: 31112379.

Prognosis: Prognosis is variable but it is generally better than in IPF.

2. Cryptogenic organizing pneumonia (COP) (previously known as bronchiolitis obliterans organizing pneumonia [BOOP]): Organizing pneumonia can be idiopathic (referred to as COP) or secondary to drugs, connective tissue disease, or viral infections (then preferentially called “organizing pneumonia”). The onset of the disease can be similar to an acute viral flu-like infection, with cough, dyspnea, fever, malaise, loss of appetite, and weight loss. Symptoms are normally present for <2 months. Physical examination usually discloses focal sparse crackles but may be normal. Chest radiographs reveal unilateral or bilateral patchy consolidation. HRCT most often reveals patchy consolidations with subpleural or peribronchial localization and associated ground-glass opacities. Radiologic changes have a tendency to migrate, changing in size and location, even without treatment. Characteristic histologic features include intraluminal fibrotic buds seen in respiratory bronchioles, alveolar ducts, and alveoli.

Treatment: Glucocorticoid therapy (prednisone 0.75-1 mg/kg) results in a complete clinical, radiographic, and physiologic recovery in approximately two-thirds of patients. High-dose therapy has to be maintained for 4 to 8 weeks with a subsequent gradual taper over the following 9 to 12 months. In case of relapse prolong the treatment and consider addition of a second immunosuppressive agent.

3. Acute interstitial pneumonia (AIP): Classically described in previously healthy individuals, AIP is a rare fulminant lung injury that presents acutely (days to weeks). A prodromal flulike illness prior to disease onset is commonly encountered. Signs include fever, tachypnea, tachycardia, cyanosis, and diffuse crackles over the lungs. In the majority of patients respiratory failure develops rapidly and mechanical ventilation is required. Chest radiographs typically demonstrate diffuse bilateral air-space disease. HRCT features include bilateral multifocal or diffuse areas of consolidative changes and ground­-glass opacities. A surgical lung biopsy may be required to confirm the diagnosis; however, the severity of illness often precludes this intervention. On histopathologic examination, AIP is characterized by a diffuse alveolar damage (DAD) pattern. AIP should be differentiated from severe infection or aspiration, acute respiratory distress syndrome, acute exacerbation of IPF, acute exacerbation of a connective tissue disease, or toxic drug reaction.

Treatment: Treatment is mainly symptomatic; mechanical ventilation may be required. Empiric antibiotic therapy is usually given due to the clinical/radiographic similarities of AIP with acute infection. Pulse-dose glucocorticoids are used in the early phase of the disease (eg, our practice is to use IV methylprednisolone 1 g once daily for 3 days followed by lower doses tapered according to the clinical response).

Prognosis: Mortality is estimated at 50%, with the majority of patients dying within 3 months of presentation. Survivors can experience disease relapse and a chronic progressive fibrotic ILD.

4. Respiratory bronchiolitis–associated interstitial lung disease (RB-ILD)/desquamative interstitial pneumonia (DIP): These diseases represent a distinct clinical entity, which is found almost exclusively in cigarette smokers between their third and sixth decades of life. The cardinal feature of RB-ILD is the accumulation of pigmented alveolar macrophages within the respiratory bronchioles with extension into alveolar ducts. DIP is characterized by the uniform filling of the alveolar spaces by cohesive clusters of pigmented alveolar macrophages and inflammatory cells. The presentation is insidious, with exertional dyspnea and persistent nonproductive cough. Coarse bibasilar crackles are frequently observed. Chest radiographs are often normal in RB-ILD, with only occasional bronchial wall thickening or reticular opacities. Key HRCT features of RB-ILD include patchy ground-glass opacities predominant in the upper lung zone and centrilobular nodularity. In DIP chest radiograph abnormalities are nonspecific and include middle- to lower-lung field air-space opacities. HRCT findings in DIP include basal ground-glass attenuation with tiny thin-walled cysts noted in the ground-glass areas in 60% of patients. RB-ILD and DIP are related conditions that may reflect different stages of the same process. As such, overlap between clinical, radiographic, and pathologic features is common.

Treatment: Smoking cessation is absolutely indicated and usually results in improvement of clinical symptoms, gas transfer, and radiographic abnormalities. Glucocorticoids can be considered for patients with recurrent or refractory disease despite ongoing smoking cessation.