Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease

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 and respiratory bronchiolitis-associated interstitial lung disease

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-associated interstitial lung disease

Respiratory bronchiolitis-associated interstitial lung disease (RBILD) can be viewed as an exaggerated respiratory bronchiolitic response to cigarette smoke. The histologic, high-resolution computed tomographic (HRCT) and bronchoalveolar lavage (BAL) features of RBILD overlap substantially with those of respiratory bronchiolitis, with the diagnosis of RBILD being based upon the severity of disease, as judged by symptoms, clinical signs, the severity of lung function impairment, and the extent of abnormalities on HRCT. Typical histologic appearances consist of an accumulation of pigmented macrophages within respiratory bronchioles, associated with peribronchial chronic inflammatory cell infiltration and, variably, peribronchial fibrotic alveolar septal thickening. Characteristic HRCT findings include poorly defined centrilobular micronodules, patchy limited ground-glass attenuation, bronchial wall thickening, and areas of regional hypoattenuation. The ventilatory defect is often mixed but is usually predominantly restrictive. The diagnosis of RBILD is often made on clinical and HRCT criteria, with BAL findings providing useful diagnostic support, but a thoracoscopic biopsy continues to be required when other features are atypical. RBILD may regress with discontinuation of smoking but often persists with no functional improvement despite smoking cessation and treatment. Nonetheless, the course tends to be benign, without inexorable deterioration. This article outlines the rationale for viewing RBILD and desquamative interstitial pneumonia as separate entities, rather than two ends of the same disease spectrum (based upon overlapping histologic and HRCT features).     

呼吸性细支气管炎伴间质性肺病和脱屑性间质性肺炎的比较分析

目的　探讨呼吸性细支气管炎伴间质性肺病 (RBILD)的临床病理特点以及与脱屑性间质性肺炎 (DIP)的关系。方法　回顾性分析 1例经电视胸腔镜肺活检诊断为RBILD患者的临床表现、影像学和组织病理学特点、糖皮质激素治疗的效果和随访结果 ,并与 1例病理学确诊的DIP患者进行比较。结果　 2例患者均为 5 7岁男性 ,吸烟史分别为 2 4、30年。临床表现为咳嗽、咯痰、气促 ,双下肺闻及veclro音 ;肺功能检查显示RBILD患者为混合型通气功能障碍 ,DIP患者为限制性轻度通气功能障碍。胸部X线片显示 2例患者双肺均有散在斑点状、斑片状密度不均阴影 ;高分辨率CT表现为两肺散在分布的间质增厚影 ,部分呈网格状改变 ,以外周和下肺为主 ,DIP患者有磨玻璃影。病理特征 :RBILD表现为在呼吸性细支气管及周围气腔内有大量均一的含色素的巨噬细胞聚集 ,肺间质有轻度的纤维组织增生和慢性炎症 ;DIP的上述病变更明显和弥漫。 2例患者均对糖皮质激素治疗反应良好 ,经随访 3年余 ,患者病情稳定无复发。结论　RBILD和DIP在临床表现上不易区分 ,而开胸肺活检组织病理学检查可区分和明确诊断 ,两者有相似之处 ,可能为同一疾病实体。     

Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)

Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) designates interstitial lung changes in smokers, characterized histologically by bronchiolocentric accumulation of pigmented alveolar macrophages and fibrotic or cellular inflammatory changes of pulmonary interstitium. The definition is nearly identical to that of condensate pneumopathy, smoker's pneumopathy or smoker's lung, defined by accumulation of pigmented alveolar macrophages with bland alveoloseptal or peribronchial fibrosis and cellular inflammation of the bronchial wall. In addition to respiratory bronchiolitis, which is found in nearly all smokers, RB-ILD comprises a broad spectrum of varying degrees of the interstitial reaction to the exogenous injury of inhalation smoking with gradual transition to desquamative interstitial pneumonia (DIP). In most cases RB-ILD manifestations are subclinical and detected coincidentally. Radiographic features are reticulonodular and ground glass opacities of the lung. The high resolution computed tomography reveals centrilobular nodules, ground glass opacities, thickening of bronchial walls, and in some cases a reticular pattern. Mild emphysema is frequent. Lung function analysis reveals only minor restrictive or obstructive defects in most cases, often combined with hyperinflation. CO diffusing capacity is slightly to moderately impaired. Pronounced interstitial lung diseases with serious restrictive defects and arterial hypoxemia have been reported infrequently. In differential diagnosis smoking related interstitial lung diseases (DIP, Langerhans cell histiocytosis, idiopathic pulmonary fibrosis) and other interstitial lung diseases have to be excluded. In most cases diagnosis can be achieved by bronchoalveolar lavage and transbronchial lung biopsy. In cases of pronounced interstitial lung disease or assumption of an additional interstitial lung disease besides RB-ILD a thoracoscopic or open lung biopsy can be necessary. RB-ILD has a favourable prognosis. After smoking cessation lung changes are reversible. Corticosteroid therapy is not necessary. A fatal outcome of RB-ILD has not been reported. Follow-up examinations are advisable in order to preclude other interstitial lung diseases. RB-ILD seems to be more frequent than it is assumed at present. The clinical picture is masked in most cases by the concomitant smoking induced chronic bronchitis. Thus only pronounced cases with structural changes and resulting differential diagnostic problems are diagnosed.     

Three cases of respiratory bronchiolitis-associated interstitial lung disease (RB-ILD): a study of HRCT-pathologic correlation]

Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a clinicopathologic entity occurring rarely in smokers. We report three cases of RB-ILD diagnosed pathologically by surgical lung biopsy. Cough was observed in all cases, sputum in one case and dyspnea on exertion in another. Reduction of diffusing capacity was observed in all three cases. No abnormality was found in the chest radiographs of any case. However, in high-resolution computed tomography (HRCT), ground-glass opacities and centrilobular nodules were observed in all three cases, emphysema in one case, intralobular linear or reticular opacities in two cases, small subpleural cysts in two and emphysema in one. Histologic examination of lung biopsy specimens taken by thoracoscopy showed peribronchiolar fibrosis and centrilobular intraluminal accumulation of macrophages in all three cases, centrilobular emphysema, membranous bronchioles filled with mucus and macrophages, and focal microscopic honeycombing in subpleural lesions in one case each. RB-ILD should be included in the differential diagnosis of interstitial lung disease in smokers.     

Persistence of abnormal bronchoalveolar lavage findings after cyclophosphamide treatment in scleroderma patients with interstitial lung disease

OBJECTIVE: Bronchoalveolar lavage (BAL) is a procedure for sampling the terminal airspace cell population to diagnose alveolitis, a condition that predicts changes in lung function in scleroderma patients. Cyclophosphamide (CYC) stabilizes the progression of lung disease in some, but not all, patients with active alveolitis. However, it is unknown whether the BAL fluid cell count obtained after CYC treatment of alveolitis predicts long-term lung function outcomes and can therefore be used to assist in therapeutic decision-making. The purpose of this study was to determine whether CYC therapy for active lung disease alters BAL fluid neutrophil and eosinophil counts and whether the persistence of abnormal BAL findings after CYC therapy predicts a decline in lung function in patients with scleroderma and interstitial lung disease (ILD). METHODS: We systematically reviewed the records of scleroderma patients who had active ILD, as evidenced by neutrophilia or eosinophilia on BAL fluid analysis before CYC therapy and on repeat analysis after completion of CYC. Pulmonary function tests (PFTs) were performed before initiation of therapy, at completion of therapy, and during long-term followup (mean +/- SD 3.6 +/- 1.94 years). RESULTS: Of the 25 study patients, in only 6 did the BAL fluid cell counts normalize after CYC therapy. No significant differences were observed between the proportions of patients who had a > or =10% decline in the % predicted DLCO or FVC on the second set of PFTs and had abnormal findings on followup BAL fluid analysis. During long-term followup, patients with persistent alveolitis had a decline in lung function (mean +/- SD change in % predicted FVC -0.6 +/- 10.8 liters and mean +/- SD change in % predicted DLCO -4.7 +/- 21.43 ml/minute/mm Hg), but their lung function did not significantly differ from that in patients whose BAL fluid cell counts had normalized (P = 0.70 and P = 0.62, respectively). CONCLUSION: Persistently abnormal results on BAL fluid analysis following CYC treatment is a common finding and does not predict a subsequent decline in lung function.     

Imaging findings in interstitial lung disease

Imaging is an essential step in the management of patients with interstitial lung disease, contributing to detection, diagnosis, evaluation of pulmonary damage and prognosis, surveillance, and screening for complications. The chest x-ray is the fundamental examination. High-resolution computed tomography is often useful, particularly for severe forms and for cases of difficult diagnosis. It should not however be used as a routine examination for the initial work-up nor repeated systematically. Computed tomography is more contributory to the diagnosis of subacute or chronic interstitial pneumonia than for acute forms. We present here the different imaging methods, the role of imaging in chronic and acute interstitial pneumonia, and discuss the main computed tomographic signs of chronic interstitial lung disease.     

Decrease in lung recoil pressure after cessation of smoking.

Tests of lung mechanics and single-breath carbon monoxide diffusing capacity (DLCO) were done in 26 apparently healthy cigarette smokers before and 2 months after cessation of smoking. There was a significant increase in vital capacity and 1-sec forced expiratory volume as well as improvement in frequency dependence of lung dynamic compliance. Slope and phase III and density dependence of maximal expiratory flow showed a borderline improvement DLCO did not change. Static lung pressure-volume curves showed a small but significant (P less than 0.01) shift toward lower pressures. We concluded that the previously reported decrease in lung recoil pressure observed in smokers is even more accentuated after cessation of smoking.     

High-resolution CT scan findings in patients with symptomatic scleroderma-related interstitial lung disease

BACKGROUND: Lung disease has become the leading cause of mortality and morbidity in scleroderma (SSc) patients. The frequency, nature, and progression of interstitial lung disease seen on high-resolution CT (HRCT) scans in patients with diffuse SSc (dcSSc) compared with those with limited SSc (lcSSc) has not been well characterized. METHODS: Baseline HRCT scan images of 162 participants randomized into a National Institutes of Health-funded clinical trial were compared to clinical features, pulmonary function test measures, and BAL fluid cellularity. The extent and distribution of interstitial lung disease HRCT findings, including pure ground-glass opacity (pGGO), pulmonary fibrosis (PF), and honeycomb cysts (HCs), were recorded in the upper, middle, and lower lung zones on baseline and follow-up CT scan studies. RESULTS: HRCT scan findings included 92.9% PF, 49.4% pGGO, and 37.2% HCs. There was a significantly higher incidence of HCs in the three zones in lcSSc patients compared to dcSSc patients (p = 0.034, p = 0.048, and p = 0.0007, respectively). The extent of PF seen on HRCT scans was significantly negatively correlated with FVC (r = - 0.22), diffusing capacity of the lung for carbon monoxide (r = - 0.44), and total lung capacity (r = - 0.36). A positive correlation was found between pGGO and the increased number of acute inflammatory cells found in BAL fluid (r = 0.28). In the placebo group, disease progression was assessed as 30% in the upper and middle lung zones, and 45% in the lower lung zones. No difference in the progression rate was seen between lcSSc and dcSSc patients. CONCLUSIONS: PF and GGO were the most common HRCT scan findings in symptomatic SSc patients. HCs were seen in more than one third of cases, being more common in lcSSc vs dcSSc. There was no relationship between progression and baseline PF extent or lcSSc vs dcSSc. Trial registration: Clinicaltrials.gov Identifier: NCT00004563.     

Total respiratory resistance and reactance in patients with diffuse interstitial lung disease

In 54 patients with interstitial lung diseases and no signs of airway obstruction we measured lung volumes, maximal expiratory flows, diffusing capacity (DLCO), total respiratory resistance (Rrs) and reactance (Xrs) between 4 and 26 Hz by means of the forced oscillation technique. In all patients DLCO was less than 75% of the expected value. Patients were classified into two groups depending on total lung capacity (TLC): group A with TLC less than 80% of expected, and group B with TLC of 80% or more. Group A demonstrated a decrease of Xrs especially at low frequencies, with small, not significant changes in Rrs. In the patients in this group with the lowest values of TLC (less than 50%), we observed an increase of Rrs at low frequencies causing a negative frequency dependence of Rrs. In group B no distinct changes of Rrs and Xrs occurred. Canonical correlation analysis between routine lung function data and forced oscillation parameters, showed tight correlations between TLC in absolute value or VC in percent of the predicted value on the one hand and average level of Xrs and average slope of Xrs (and Rrs) vs frequency curves on the other hand. Measurements of lung mechanics in five additional patients and comparison with a model of the respiratory system suggest that the changes of Rrs and Xrs are not explained totally by the observed increase in lung tissue resistance and decrease in lung compliance. The observed changes in Rrs and Xrs are not specific for restrictive lung disorders; similar changes are met also in moderately advanced obstructive diseases.     

心血管疾病患者戒烟效果的影响因素

目的 分析心血管疾病患者戒烟效果的影响因素。 方法 心血管内科住院的吸烟患者在接受戒烟健康教育后随访观察12个月，按戒烟效果分为戒烟有效组（n = 156）和戒烟无效组（n = 188）, 采用病例对照研究方法分析戒烟效果的影响因素。 结果 单因素分析显示年龄>70岁、冠心病、高血压病和心功能不全患病率高及既往每日吸烟数量少（≤10 支/d）的人群戒烟有效率显著增高（均P<0.01）；独居及接触吸烟的患者戒烟有效率显著降低（均P<0.01）。多因素Logistic回归分析显示患有冠心病、心功能不全、独居、接触吸烟者及每日吸烟数量少均是戒烟效果的独立影响因素，患有冠心病，心功能不全和每日吸烟数量少能提高戒烟有效率，而独居和接触吸烟者降低戒烟有效率。 结论 患者患有严重疾病有利于提高戒烟有效率，但独居和接触吸烟者不利于提高戒烟有效率。     

Gefitinib-induced interstitial lung disease showing improvement after cessation: disassociation of serum markers

Gefitinib (ZD1839), a small-molecule epidermal growth factor receptor tyrosine kinase inhibitor, is an anticancer agent for patients with non-small cell lung carcinoma. Recently, however, as a result of accumulating evidence, it has been recognized that gefitinib can give rise to lethal lung toxicity. The authors report a case of interstitial lung disease (ILD) induced by gefitinib, which improved promptly following cessation of the administration of the agent. Clinical signs suggesting a good prognosis were noted, namely, findings similar to acute eosinophilic pneumonia on CT and a disassociation in the elevation of specific serum markers of ILD. At the time of onset of ILD, serum concentrations of surfactant protein (SP)-A and SP-D were significantly increased, whereas that of KL-6 was not increased. A previous study of three cases of lethal lung toxicity resulting from gefitinib administration revealed a significant and almost equal increase in KL-6, SP-A and SP-D. These results suggest that SP-A and SP-D may be indicators of gefitinib-induced ILD and that KL-6 is a predictor of outcome. Using a combination of these markers may help to establish a differential prognosis in patients with gefitinib-induced ILD.     

类风湿关节炎继发间质性肺疾病患者胸部高分辨率CT和生活质量的研究

目的 观察治疗前后类风湿关节炎(RA)继发间质性肺疾病( ILD)患者胸部高分辨率CT( HRCT)和生活质量的变化及与HRCT相关的主要因素.方法 26例初治RA-ILD患者,观察治疗前、治疗12周及24周临床特征、HRCT、生活质量的变化,治疗前后指标变化采用重复测量资料的方差分析,用多元回归的方法分析HRCT与其他指标的相关性.结果 26例患者中男性12例(46％).随访24周,11例出现肺部感染,发生率42％.激素联合环磷酰胺治疗24周,HRCT评分(8±6)较治疗前(12±5)明显好转,治疗12周HRCT显示12例有吸收,治疗24周16例有吸收,6例无明显变化,4例进展.治疗后患者生活质量圣乔治呼吸问卷(SGRQ)中影响分、症状分、活动分、总均分明显下降(F=3.783,6.362,4.217,4.426;均P＜0.05),健康状况调查问卷(SF-36)中身体和精神健康各项指标均较治疗前明显提高(P＜0.01).HRCT的相关因素:治疗前SGRQ中影响分(P=0.000)、症状分(P=0.001)、SF-36中精力(P=0.012)、球蛋白(P=0.027);治疗24周SGRQ中症状分(P=0.001)、病程(P=0.002)、英国医学研究会呼吸困难量表(MRC)气促分级(P=0.011)、SF-36中精力(P=0.036).结论 男性RA易继发ILD,RA-ILD易出现肺部感染,早期治疗后大部分患者胸部HRCT有吸收,生活质量明显提高.呼吸道症状、气促程度、球蛋白、病程及患者的精力与HRCT明显相关.     

重视冠心病患者吸烟干预

WHO估计到2025年将有1000万人死于吸烟引起的相关疾病.在15～59岁人群中,61%的疾病负担归因为吸烟.在过去的几十年,中国男性的吸烟率虽然有所下降,如2000-2001年成人男性吸烟率为60.2%[1],第四次国家卫生服务调查显示,2008年15岁以上人口男性吸烟率为48.0%,但吸烟仍然是我国公共卫生重大问题之一.     

Success of smoking cessation in patients with chronic obstructive pulmonary disease

Smoking causes chronic obstructive pulmonary disease (COPD) in 15 to 20% of smokers. Smoking accelerates the annual rate of FEV(1) decline, whereas it was demonstrated that smoking cessation is the major factor that reduces this decline. The aims of this prospective study were to assess the success rate and factors affecting smoking cessation, besides, to evaluate the effect of cessation on annual FEV(1) decline. Sixty-five consecutive patients with COPD and as a control group 50 ageand sex-matched healthy smokers who were admitted to our smoking cessation clinic were enrolled in the study. Intensive behavioral therapy alone or with nicotine replacement therapy or bupropion HCL was given to both groups and success rate of smoking cessation after one year was assessed. It was shown that demographic features of the subjects and the history of COPD had no effect on success of smoking cessation. At the end of one year the rate of smoking cessation was 29% in patients with COPD and 49% in the control group (p< 0.05). All different therapy interventions had similar effects on smoking cessation. The annual FEV(1) values increased 29 mL in quitters and decreased 25 mL in patients continuing smoking (p> 0.05). In this study, we concluded that the success of smoking cessation in COPD patients admitted to the smoking cessation clinic was significantly lower than healthy smokers and annual FEV(1) decline was decreased in quitters.