Histopathologic classification plays a key role in separating multiple forms of idiopathic interstitial pneumonia into clinically meaningful categories with important differences in natural history, prognosis, and treatment. Microscopic criteria in diagnosis of these entities include the pattern and microanatomic distribution of inflammation, fibroblast proliferation, collagen deposition, and architectural remodeling. Usual interstitial pneumonia (UIP) defines idiopathic pulmonary fibrosis and is the most common of the idiopathic interstitial pneumonias. UIP has distinctive morphologic features that allow precise diagnosis in classical cases. Other forms of idiopathic interstitial pneumonia include desquamative interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, acute interstitial pneumonia, and nonspecific interstitial pneumonia. These latter categories differ from UIP in that the histopathologic findings do not, by themselves, allow specific diagnosis in most cases and require careful correlation with clinical and radiologic findings.

Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease.Chest. 2005 Jan;127(1):178-84.

BACKGROUND: Desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) are uncommon forms of interstitial lung disease and have been incompletely characterized. STUDY OBJECTIVES: To further characterize the clinical features and course of subjects with DIP and RB-ILD. DESIGN: Retrospective study. SETTING: Tertiary care, referral medical center. PATIENTS: Twenty-three subjects with DIP and 12 subjects with RB-ILD seen over a 12-year period between 1990 and 2001. INTERVENTIONS: None. RESULTS: The study population included 19 men (54%) and 16 women (46%). The mean (+/- SD) age at diagnosis was 46 +/- 10 and 43 +/- 7 years, respectively, for patients with DIP and RB-ILD. All subjects were either current or previous smokers except for three subjects with DIP. The diagnosis was confirmed in all cases by surgical lung biopsy. Bronchoscopy with transbronchial lung biopsy had been performed in 12 patients and was nondiagnostic in all. The most common pulmonary function abnormality was a reduced diffusing capacity of the lung for carbon monoxide. A CT scan of the chest revealed ground-glass opacities bilaterally in most patients who had DIP and RB-ILD. No differences were observed between subjects with DIP and RB-ILD with respect to clinical features, radiologic findings, or pulmonary function test results. The clinical course was characterized by relative stability in the majority of patients in both groups and a partial response to corticosteroid therapy. Five deaths were observed, including three resulting from progressive diffuse lung disease, all in subjects with DIP. CONCLUSIONS: We concluded that DIP and RB-ILD are chronic disease processes that in most patients are related to smoking. Persistent abnormalities can be seen on pulmonary function testing and radiologic studies despite smoking cessation and corticosteroid therapy. Corticosteroid therapy appeared to be associated with modest clinical benefit but usually not with resolution of disease. Progressive disease with eventual death can occur in subjects with DIP, especially with continued cigarette smoking.

Desquamative interstitial pneumonia, respiratory bronchiolitis and their relationship to smoking. Histopathology. 2004 Sep;45(3):275-82.

AIMS: Respiratory bronchiolitis (RB) and desquamative interstitial pneumonia (DIP) are closely associated histological patterns of interstitial pneumonia, although there are no studies on the extent of individual histological parameters. Furthermore, the term smoking related-interstitial lung disease (SR-ILD) has been proposed as a term to encompass patients with both these histological patterns who give a history of smoking, though it is not well defined how this term relates to historical cases of DIP. The aim of this study was to compare histological parameters in cases of DIP and RB and then to review in detail clinical, imaging and histological data for DIP in relation to a history of smoking. METHODS AND RESULTS: Forty-nine cases were reviewed, 24 with RB and 25 with DIP; five cases of DIP were re-classified as RB on review due to bronchocentricity of the infiltrate. There was a significantly greater extent of interstitial fibrosis (P = 0.02), lymphoid follicles (P < 0.001) and eosinophilic infiltration (P < 0.0001) in patients with DIP compared with RB. In addition, the extents of these three parameters were significantly interrelated. Patients with DIP had a lower incidence of smoking (60%) when compared with patients with RB-ILD (93%) (P < 0.005). Further analysis of smokers versus never-smokers with DIP showed no difference in histological parameters, extent of haemosiderin deposition or the number of CD1a+ macrophages between the two groups, nor were there any differences in clinical data to suggest other aetiologies. Follow-up high-resolution computed tomography data from patients with DIP suggested that a pattern of fibrotic non-specific interstitial pneumonia (NSIP) may develop in the long term in both smokers and never-smokers. CONCLUSION: There are significant differences in the extent of interstitial fibrosis, lymphoid follicles and eosinophilic infiltration between DIP and RB, as well as a much lower incidence of smoking in patients with DIP. Whether the lower reported incidence of smoking in DIP reflects referral bias or conservatism in giving a history of smoking remains uncertain, as neither histological parameters nor clinical data indicate a difference between smokers and never-smokers with DIP. Nevertheless, some cases of DIP are likely to remain idiopathic and unrelated to RB, though still have a good prognosis. Furthermore, they may evolve into a pattern resembling fibrotic NSIP. Therefore, whilst SR-ILD is appropriate in the correct clinical setting, the distinction between the histological patterns of RB and DIP remains appropriate.

Comparative analysis of respiratory bronchiolitis-associated interstitial lung disease and desquamative interstitial pneumonia.Zhonghua Jie He He Hu Xi Za Zhi. 2004 Jun;27(6):373-7.

OBJECTIVE: To investigate the clinicopathologic characteristics of respiratory bronchiolitis-associated interstitial lung disease (RBILD) and its relationship to desquamative interstitial pneumonia (DIP). METHODS: The clinical and pathological data of one patient with RBILD confirmed by video-assisted thoracoscopic lung biopsy were reviewed retrospectively, and compared with one patient with DIP. RESULTS: Both patients were 57 year old male, and they had a history of cigarette smoking for 24 and 30 years respectively. The clinical manifestations were cough and sputum production, breathlessness with exertion, and crackles on chest examination. Lung function test showed a mild abnormality with mixed obstructive-restrictive and restrictive pattern respectively. The chest radiograph showed scattered small nodules and patchy densities. High resolution computer tomography showed scattered interstitial infiltrates and reticular changes in the middle and lower lung fields, but patchy ground-glass attenuation was found only in DIP. The pathological examination showed the presence of clusters of pigmented macrophages within the lumens of respiratory bronchioles, alveolar ducts and peribronchiolar alveolar spaces, with patchy submucosal and peribronchiolar infiltration of lymphocytes and histiocytes. Mild peribronchiolar fibrosis was found in RBILD. Compared with RBILD, the lesions of DIP were more severe and widespread. Both the patients responded favorably to glucocorticoids. They were followed for more than three years. CONCLUSION: RBILD could be confused with DIP in clinical manifestations, but can be separated by open lung biopsy. Considering their similarities, these two lesions may be regarded as a same disease entity.

DIP (desquamative interstitial pneumonia): as a tobacco-associated disease -- case report. Rev Port Pneumol. 2004 Sep-Oct;10(5):431-5.

DIP (desquamative interstitial pneumonia) is an interstitial lung disease with diffuse and uniform accumulation of alveolar macrophages. There is a strong association with tobacco since 90% of the patients are smokers. The interstitial lung diseases related to tobacco are diverse and include tumours, emphysema, chronic bronchitis, RBILD (Respiratory Bronchilites associated Interstitial Lung Disease), DIP and Langerhans Cell Histiocitosis. The authors present a case of DIP. A brief theorycal revision and discussion of a case is made facing the association with tobacco.

A case of completely resolved pneumatocoeles in desquamative interstitial pneumonia. Respirology. 2003 Sep;8(3):389-95.

Desquamative interstitial pneumonia (DIP), also known as alveolar macrophage pneumonia (AMP), represents a subset of idiopathic interstitial pneumonia that responds better to steroids and has a more favourable prognosis than usual interstitial pneumonia. Recently, we encountered a case of DIP with the formation of multiple pulmonary cysts during corticosteroid maintenance treatment. After the introduction of cyclophosphamide, the cysts gradually disappeared. This complete resolution is believed to have resulted from the clearance of check-valve-like bronchiolar obstructions that may be another interesting terminal airway pathology in DIP.

BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia. Eur Respir J. 2003 Aug;22(2):239-44.

Idiopathic pulmonary fibrosis (IPF), which has the histological pattern of usual interstitial pneumonia (UIP), is a progressive interstitial lung disease with a poor prognosis. Idiopathic interstitial pneumonias with a histological pattern of nonspecific interstitial pneumonia (NSIP) have a better prognosis than UIP, and may present with a clinical picture identical to IPF. The authors hypothesised that bronchoalveolar lavage (BAL) findings may distinguish between UIP and NSIP, and have prognostic value within disease subgroups. BAL findings were studied retrospectively in 54 patients with histologically proven (surgical biopsy) idiopathic UIP (n=35) or fibrotic NSIP (n=19), all presenting clinically as IPF. These findings were also compared with the BAL profile of patients with other categories of idiopathic interstitial pneumonias. BAL total and differential cell counts did not differ between the two groups. Survival was better in NSIP. In neither group were BAL findings predictive of survival or changes in lung function at 1 yr, even after adjustment for disease severity, smoking and treatment. BAL differential counts in fibrotic NSIP differed from respiratory bronchiolitis-associated interstitial lung disease, but not from desquamative interstitial pneumonia or cellular NSIP. The authors conclude that bronchoalveolar lavage findings do not discriminate between usual interstitial pneumonia and nonspecific interstitial pneumonia in patients presenting with clinical features of idiopathic pulmonary fibrosis, and have no prognostic value, once the distinction between the two has been made histologically.

Desquamative interstitial pneumonia--case report and review of literature. Nihon Kokyuki Gakkai Zasshi. 2002 Feb;40(2):160-5.

A 50-year-old man was admitted to our hospital because diffuse reticulonodular shadows in the bilateral lung fields had deteriorated on chest radiographs during a regular checkup. The bronchoalveolar lavage (BAL) fluid revealed an increase in the total number of cells, including slightly elevated levels of eosinophils and neutrophils. The thoracoscopic lung biopsy specimens showed findings compatible with desquamative interstitial pneumonia (DIP). Corticosteroid therapy was done, and improvement of chest CT findings and pulmonary function were seen. We reviewed the clinical features in seventeen patients with biopsy-proven DIP reported in Japan. All patients have good prognoses and a high frequency of steroid responsiveness. Moreover, many patients were positive for antinuclear antibodies in serological tests, and there was a tendency toward increasing eosinophils in BAL fluids.

Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease.Semin Respir Crit Care Med. 2001 Aug;22(4):387-98.

Our understanding of the various types and patterns of diffuse lung disease that might result in fibrosis has evolved considerably over the last 50 years. Many entities now regarded as distinct had been previously "lumped'' together as a single disease, "lung fibrosis,'' and more recently misdiagnosed as idiopathic pulmonary fibrosis (IPF, synonymous with cryptogenic fibrosing alveolitis). In 1965 desquamative interstitial pneumonia (DIP) was first described, and later it was clearly demonstrated that the clinical and pathological features of DIP and IPF were different, particularly in terms of survival and response to therapy. They are not part of the same disease spectrum nor does DIP evolve into usual interstitial pneumonia (UIP). Later, in the mid-1980s, RBILD was described as a distinct clinicopathologic syndrome with features consistent with an interstitial lung disease among current or former smokers. In the recent histopathological classification of idiopathic interstitial pneumonia (IIP), DIP and RBILD have been included as separate entities, although there is some evidence that suggests they may lie at the two ends of a single spectrum. The debate bears similarities with the debate about DIP and UIP and is as yet unresolved. This article will give a broad and current overview of these two rarer forms of IIP, including issues that relate to diagnosis, imaging, histopathology, treatment, and prognosis.

Respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, and desquamative interstitial pneumonia: different entities or part of the spectrum of the same disease process?AJR Am J Roentgenol. 1999 Dec;173(6):1617-22.

OBJECTIVE: Our objective was to assess high-resolution CT findings of respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, and desquamative interstitial pneumonia and to determine whether these three entities could be reliably differentiated by radiologic criteria. MATERIALS AND METHODS: CT scans (1- to 3-mm collimation) were reviewed in 40 patients with pathologically proven respiratory bronchiolitis (n = 16), respiratory bronchiolitis-associated interstitial lung disease (n = 8), or desquamative interstitial pneumonia (n = 16). All patients with respiratory bronchiolitis and respiratory bronchiolitis-associated interstitial lung disease were cigarette smokers, and 85% of the patients with desquamative interstitial pneumonia had a history of smoking. CT scans were independently reviewed by two radiologists who assessed the pattern and distribution of abnormalities. RESULTS: The predominant abnormalities in respiratory bronchiolitis were centrilobular nodules (12 [75%] of 16 patients) and ground-glass attenuation (six [38%] of 16). No single abnormality predominated in the respiratory bronchiolitis-associated interstitial lung disease group; findings included ground-glass attenuation (four [50%] of eight), centrilobular nodules (three [38%] of eight), and mild fibrosis (two [25%] of eight). All patients with desquamative interstitial pneumonia showed ground-glass attenuation, and 10 (63%) of the 16 showed evidence of fibrosis. CONCLUSION: The significant overlap between the CT findings of respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, and desquamative interstitial pneumonia is consistent with the concept that they represent different degrees of severity of small airway and parenchymal reaction to cigarette smoke.

Spontaneous remission of desquamative interstitial pneumonia.Intern Med. 1997 Oct;36(10):728-31

We report a case of spontaneous remission of desquamative interstitial pneumonia (DIP) in a 50-year-old male. The histological diagnosis of DIP was based on open lung biopsy. A chest X-ray revealed reticulo-nodular shadows in the bilateral lung fields, and the patient had mild dyspnea on exertion. Without treatment, these shadows decreased gradually and disappeared after several months. The patient recovered completely within one year, and recurrence of the disease has not been observed for 4 years. Recently, DIP has rarely been described, and the spontaneous remission of DIP has not been reported since Carrington et al in 1978 (1).

Fibrosing alveolitis and desquamative interstitial pneumonitis.Pediatr Pulmonol. 1994 Jun;17(6):359-65.

We report the experience with and evaluation of treatment strategies in fibrosing alveolitis and desquamative interstitial pneumonitis (FA/DIP) over the last 16 years by a review of all cases referred to a tertiary referral center. There were 25 cases, 16 boys and 9 girls (mean age at onset, 2.3 years; range, 7 days to 11.6 years). In each case the diagnosis was confirmed by open lung biopsy at a mean age of 3.3 years (range, 7 weeks to 15.1 years). Presently features were tachypnea (19), cyanosis (15), cough (12), exertional dyspnea (7), recurrent chest infections +/- wheezing (9), and clubbing (8). Four patients recovered without antiinflammatory medication. The others received specific treatment. Of 11 patients given only prednisolone, six improved, two did not, and three died despite treatment. Of five patients receiving only chloroquine, four responded. Five patients received both prednisolone and chloroquine; one died, two responded well. There was poor progress in the remaining two. Of the 10 patients receiving chloroquine six (60%) showed a good response. A younger presentation carried a worse prognosis, but chest radiology at presentation and outcome were not interrelated. Those with mild histological changes all survived, but severe desquamation or fibrosis at biopsy was not related to outcome. In four cases there was a family history (16%). Patients with FA/DIP probably represent a disease spectrum of multiple etiology with a variable prognosis and response to treatment.

Desquamative interstitial pneumonia: a case presentation. Md Med J. 1993 Nov;42(11):1119-22

A 25-year-old African-American woman presented in the emergency room of a community hospital complaining of shortness of breath. The patient was admitted with a diagnosis of atypical pneumonia. Her respiration worsened despite intravenous erythromycin, nebulized albuterol, 40% oxygen via ventimask, and guaifenesin. An open lung biopsy revealed pulmonary tissue showing interstitial fibrosis with lymphocytes and histiocytes scattered within the fibrous tissue. Numerous alveoli contained mononuclear cells as seen in desquamative interstitial pneumonia. The patient did not respond to methylprednisolone and died on the eighteenth hospital day.