Showing papers on "Interstitial lung disease published in 1998"
TL;DR: The clinical and pathologic features of asbestosis and silicosis, and mineralogic features of asbestos and silica that may be important in disease causation along with confounding factors such as coexposures to smoking and/or other mineral dusts are considered.
Abstract: Interstitial pulmonary fibrosis caused by the inhalation of asbestos fibers or silica particles continues to be an important cause of interstitial lung disease. Although more stringent control of asbestos in the workplace and decreasing industrial use has contributed to declines in the prevalence of asbestosis in the United States (1), new cases continue to be identified. Similarly, silicosis is seen among sandblasters, underground miners, foundry and quarry workers, and in other dust-exposed trades (2). Both diseases, which may have relatively long latency periods, are observed in the clinic today, usually as a result of high occupational exposures in the past, and they are problematic in that treatment with corticosteroids and immunosuppressants, the usual approaches to therapy for fibrotic lung disease, is ineffective (3). Asbestos and silica are complex, naturally occurring minerals that are chemically and physically distinct. Moreover, the pathology of asbestosis and silcosis is dissimilar. However, the pathogenesis of these lesions and the major changes in pulmonary architecture, namely, the laying down of collagen in an interstitial location, appear to be similar to many of the features seen in idiopathic pulmonary fibrosis (IPF). Like IPF and representative animal models of IPF such as bleomycin instillation (4), both asbestosis and silicosis are characterized by a persistent inflammatory response and generation of proinflammatory and profibrotic mediators. Although asbestosis and silicosis have been studied intensely by basic and clinical research scientists, little is known about the crucial cellular mechanisms that initiate and drive the processes of inflammation and fibrogenesis. Many laboratories have developed animal and in vitro models of asbestosis and silicosis to elucidate the cellular events and properties of minerals important in disease causation. Others have explored confounding factors contributing to particulate-induced cell injury as well as cellular and molecular defense mechanisms in response to these minerals. This information has been used to modulate inflammation and fibrosis in expermental animal models in attempts to develop more effective treatment regimens for pulmonary fibroses. This review will briefly address the clinical and pathologic features of asbestosis and silicosis, and consider the mineralogic features of asbestos and silica that may be important in disease causation along with confounding factors such as coexposures to smoking and/or other mineral dusts. The relationship of particle number, type, and size to disease patterns will be reviewed. We will then summarize data published within the past 5 yr on cellular and molecular mechanisms of asbestosis and silicosis and preventive approaches to these diseases in experimental animal models. Lastly, we emphasize in our SUMMARY AND CONCLUSIONS the common mediators and cell types affected in the pathogenesis of both mineral-related and other forms of pulmonary fibrosis and plausible interrelationships between the development of fibrosis and lung cancer, a disease linked to occupational exposures to asbestos and possibly to exposures to silica (1, 5).
885 citations
TL;DR: Patients with IPF have a high prevalence of increased esophageal acid exposure, usually without typical GER symptoms, and acid reflux may be a contributing factor in the pathogenesis of IPF.
Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease (ILD) of unknown etiology. Introduction of acid into the respiratory tree can produce pulmonary fibrosis. Gastroesophageal reflux (GER) has previously been associated with several other respiratory conditions, including pneumonia, bronchitis, and asthma. To investigate prospectively the possible association of GER and IPF, 17 consecutive patients with biopsy-proven IPF and eight control patients with ILD other than IPF underwent dual-channel, ambulatory esophageal pH monitoring. Sixteen of 17 patients with IPF had abnormal distal and/or proximal esophageal acid exposure compared with four of eight control patients (p = 0.02). In the patients with IPF, mean percent distal total (13.6 versus 3.34, p = 0.006), distal upright (12.4 versus 5.1, p = 0.04), distal supine (14.7 versus 0.88, p = 0.02), and proximal supine (7.48 versus 0.24, p = 0.04) esophageal acid exposure times were significantly greater than those in control patients. Only four patients with IPF (25%) with increased acid exposure had typical reflux symptoms such as heartburn or regurgitation. Patients with IPF have a high prevalence of increased esophageal acid exposure, usually without typical GER symptoms. GER in these patients tends to occur at night and extend into the proximal esophagus. Acid reflux may be a contributing factor in the pathogenesis of IPF.
518 citations
TL;DR: CT-determined main pulmonary artery diameter (MPAD) has excellent diagnostic value for detection of PH in patients with advanced lung disease and standard chest CT scans can be used to screen for PH as a cause of exertional limitation in Patients with parenchymal lung disease.
371 citations
TL;DR: In conclusion, idiopathic nonspecific interstitial pneumonia can be differentiated from other types of idiopATHic interstitial lung disease, both pathologically and clinically.
Abstract: Based on past difficulties in clinically differentiating patients with idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans-organizing pneumonia (BOOP), and nonspecific interstitial pneumonia/fibrosis (NSIP), which all manifest clinically as interstitial lung disease, experience with pathologically confirmed examples of the three diseases was reviewed to compare clinical profiles and prognosis and to define NSIP more clearly. Thirty-one patients (15 males and 16 females) were pathologically identified as NSIP and subclassified into either the cellular (n=16) or fibrotic group (n=15). All 31 patients were clinically considered to be idiopathic NSIP cases. Patients with idiopathic BOOP (n=16) and IPF (n=64) were compared with the NSIP patients. Subacute presentation of interstitial lung disease characterized both idiopathic NSIP and idiopathic BOOP. NSIP patients showed volume loss on a chest radiograph (29.0%) and honeycombing on a computed tomography scan (25.8%); these features were not found in BOOP patients. Bronchoalveolar lavage lymphocytosis was characteristic of both BOOP and NSIP. Two subgroups of NSIP can be recognized histologically: patients in the fibrotic group had a less favourable outcome than those in the cellular group. BOOP and NSIP had a more favourable outcome than IPF. In conclusion, idiopathic nonspecific interstitial pneumonia can be differentiated from other types of idiopathic interstitial pneumonia, both pathologically and clinically.
310 citations
TL;DR: Mortality is increased both in the SSc population as a whole and in its different subsets (dSSc and lSSc).
Abstract: OBJECTIVES To analyse survival rates and the causes of death in a systemic sclerosis (SSc) population, and to evaluate the occurrence of fatal malignant neoplasms and their possible association with oral cyclophosphamide (CYC) treatment.
METHODS Survival was calculated for 249 SSc patients followed up for up to 13 years. Mean (SD) follow up was 5.8 (4.2) years. The 49 deceased patients were subdivided according to causes of death and its relation to SSc. Fatal malignancies in CYC treated patients were compared with those occurring in non-CYC treated patients.
RESULTS The overall 5 and 10 year survival rates were 86% and 69% respectively. There was a 4.6-fold increased risk of death, as compared with the general population. Prognosis was worse in the diffuse cutaneous involvement (dSSc) and male subgroups than in the limited cutaneous involvement (lSSc) and female subgroups. Of the 49 deaths, 24 were attributable to pulmonary complications such as pulmonary fibrosis, pulmonary hypertension, pneumonia or pulmonary malignancy. Treatment with oral CYC did not increase the risk of dying of cancer.
CONCLUSIONS Mortality is increased both in the SSc population as a whole and in its different subsets (dSSc and lSSc). Prognosis is worst among male patients with dSSc. However, the 5 year survival rate was better than those reported from earlier studies. Most patients die of cardiopulmonary disease. Five of seven fatal lung cancers were adenocarcinomas, possibly caused by chronic inflammatory disease of the lung. In this study, CYC treatment was not associated with an increased incidence of fatal malignant neoplasms.
241 citations
TL;DR: A high prevalence of airway abnormalities as assessed with high-resolution computed tomography and/or pulmonary function tests was observed in rheumatoid arthritis patients and HRCT appears to be more sensitive than PFTs for detecting small airways disease.
Abstract: The aim of the present study was to assess the prevalence and characteristics of airways involvement in rheumatoid arthritis (RA) patients in the absence of interstitial lung disease. We prospectively evaluated, with high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs), 50 patients with RA (nine males and 41 females; mean age: 57.8 yr), including 39 nonsmokers and 11 smokers (mean cigarette consumption: 15.3 pack-yr) without radiographic evidence of RA-related lung changes. PFTs demonstrated airway obstruction (i.e., reduced FEV1/VC) in nine patients (18%) and small airways disease (SAD) (i.e., decreased FEF25–75, defined as exceeding the predicted value by 1.64 residual SD [RSD] or more, and/or an increased phase III slope > 2 SD by single breath nitrogen washout) in four patients (8%). HRCT demonstrated bronchial and/or lung abnormalities in 35 cases (70%), consisting of air trapping (n = 16; 32%), cylindral bronchiectasis (n = 15; 30%), mild heterogeneity in lung attenuation (...
220 citations
TL;DR: Despite its heterogeneity, NSIP deserves to be individualized as an original clinicopathologic entity and should be clearly distinguished from usual interstitial pneumonia, especially because of a better prognosis.
Abstract: Nonspecific interstitial pneumonia/fibrosis (NSIP) has recently been individualized within the group of idiopathic interstitial pneumonias mainly based on a pathologic pattern of temporally uniform lesions distinct from usual, desquamative, and acute interstitial pneumonia. We studied 12 consecutive patients with NSIP at lung biopsy done as a diagnostic procedure for idiopathic interstitial lung disease. The patients were six males and six females, aged 52.5 ± 11.8 yr. In 8 of 12 cases the pathologic lesions consisted of both cellular interstitial inflammation and fibrosis, whereas only cellular inflammation was present in three cases, and fibrosis in one. Dyspnea, cough, inspiratory crackles, and squeaks were the most common symptoms and signs. Six cases were cryptogenic. An associated disorder or a presumed cause was present in the other six patients, including underlying connective tissue disease (n = 3), organic dust exposure (n = 2), and prior acute lung injury (n = 1). Lung function tests found a re...
213 citations
TL;DR: Sjögren's syndrome is one of the most common systemic rheumatic diseases; respiratory manifestations include chronic cough, obstructive airways disease, pulmonary lymphoma, and interstitial lung disease that may progress to severe pulmonary fibrosis.
209 citations
TL;DR: A pathologic classification applicable to the surgical pathology of bronchiolitis is presented and the anatomy of the small airways is discussed, and a variety of clinical, radiologic, and functional patterns ofBronchiolar disease are presented.
Abstract: Bronchiolitis represents a cellular and mesenchymal reaction involving bronchioles. The interplay between the cellular infiltrate and the mesenchymal reaction affects the lumen size, lamina propria, muscular layer, and bronchiolar adventitia. The result is a variety of clinical, radiologic, and functional patterns of bronchiolar disease. The anatomy of the small airways is discussed, and a pathologic classification applicable to the surgical pathology of bronchiolitis is presented. The classification is practical and includes asthma, chronic obstructive pulmonary disease, cellular bronchiolitis, respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, bronchiolitis obliterans (including bronchiolitis obliterans with intraluminal polyps and constrictive bronchiolitis), dust-related small airway fibrosis, and (postinflammatory) bronchiolar scarring and peribronchiolar fibrosis.
182 citations
Journal Article•
TL;DR: It is suggested that high serum GOT and ferritin levels, presence of anti-Jo-1 antibody and characteristic microangiopathy may have predictive value and should encourage the search for pulmonary dysfunction and interstitial lung disease in patients with PM and DM.
Abstract: Objective. To assess prevalence, characteristics, and predictive factors of pulmonary involvement in polymyositis (PM) and dermatomyositis (DM). Methods. The medical records of 55 consecutive patients with PM and DM between 1983 and 1996 were reviewed. The criteria for diagnosis of PM and DM were based upon Bohan and Peter criteria. Results. Twenty-two patients (40%) developed lung impairment with a mean of 17 months after onset of PM and DM. The 3 main types of pulmonary disorders were interstitial lung disease (41%), ventilatory insufficiency with bronchopneumonia (22.8%), and alveolitis (with pulmonary function tests revealing restrictive pattern, low diffusing capacity, and normal computerized tomography) (36.2%). Both morbidity and mortality rates were as high as 40 and 27%, respectively, in PM and DM patients with lung involvement. Moreover, for the group with pulmonary diseases, serum GOT and ferritin levels were higher (p = 0.01 and p = 0.02) and the presence of anti-Jo-1 antibody and characteristic microangiopathy were more frequent (p < 0.05 and p = 0.0002). Conclusion. This series reveals both high prevalence (40%) and severity of pulmonary involvement in PM and DM. Our findings also suggest that high serum GOT and ferritin levels, presence of anti-Jo-1 antibody and characteristic microangiopathy may have predictive value and should encourage the search for pulmonary dysfunction and interstitial lung disease in patients with PM and DM.
157 citations
TL;DR: I.v. pulse CYC proved to be an effective and well-tolerated treatment in these patients and should be reserved for progressive ILD featuring indices of high inflammatory activity, since it appears to target mainly the inflammatory component of the disease.
Abstract: Objective
Substantial toxicity limits the use of daily oral cyclophosphamide (CYC) for the treatment of interstitial lung disease (ILD) due to collagen vascular diseases. We examined whether intravenous (IV) pulse CYC can be substituted for daily oral therapy.
Methods
Six patients with rapidly progressive ILD due to polymyositis, systemic sclerosis, systemic lupus erythematosus, or primary Sjogren's syndrome received 6-9 cycles of IV pulse CYC (0.5 gm/m2 of body surface area), together with an initial course of 50 mg of prednisolone, which was tapered to a maintenance dosage of 5-7.5 mg/day, and their response was measured clinically, by high-resolution computed tomography (HRCT) and by assessment of the bronchoalveolar lavage (BAL) cell profile.
Results
All patients showed significant improvement in exercise tolerance and lung function. Elevated BAL neutrophils dropped substantially, whereas the response of BAL lymphocytes was inconsistent. Low-attenuation opacities in the HRCT regressed in 4 patients and remained unchanged in 2, but reticular infiltrates remained largely unaffected. Remission was maintained with hydroxychloroquine, azathioprine, or cyclosporin A.
Conclusion
IV pulse CYC proved to be an effective and well-tolerated treatment in these patients. Since it appears to target mainly the inflammatory component of the disease, it should be reserved for progressive ILD featuring indices of high inflammatory activity.
TL;DR: The fibrotic process is an important determinant of outcome and a potential target for therapeutic intervention in the acute respiratory distress syndrome.
Abstract: The acute respiratory distress syndrome (ARDS) is an acute and severe form of microvascular lung injury which is frequently seen in intensive therapy units. Reductions in mortality have been reported by some centres; however, 40–70% of patients still die from this syndrome.1 2 Treatment at present is largely supportive and, despite our increased understanding of the pathological processes involved, there are no specific treatments of proven benefit.
Interstitial and intra-alveolar fibrosis are hallmarks of the more advanced stages of ARDS and are characterised by the abnormal and excessive deposition of extracellular matrix proteins, in particular collagen.3 4 Histologically and biochemically this is similar to the fibrosis seen in other more chronic forms of interstitial lung disease4; however, more is known of the mediators and cellular events that occur in these disorders. The decrease in pulmonary compliance and progressive hypoxia resulting from fibrotic change leads to ventilator dependence. As a result, progressive fibrosis is a direct cause of respiratory death in up to 40% of patients3 5 but is also an indirect cause of death due to nosocomial infection and progressive multi-organ failure in up to 70% of patients who die from ARDS.6 Thus, the fibrotic process is an important determinant of outcome and a potential target for therapeutic intervention.
ARDS is traditionally divided into three phases: exudative, proliferative and fibrotic (fig 1). The initial exudative phase involves the leakage of proteinaceous fluid and the migration of cells, in particular neutrophils, from the circulation into the interstitium and alveolar space following diffuse damage to the endothelial and epithelial surfaces. The proliferation of fibroblasts and type II pneumocytes characterises the second phase during which activated fibroblasts secrete a number of extracellular matrix proteins within the interstitium but also migrate into the alveolar space where they form …
TL;DR: The results of that investigation details the clinicopathologic and epidemiologic features of a previously unrecognized occupational lung disease in the nylon flocking industry, including the results of an investigation at the Rhode Island facility.
Abstract: Background: Two young men working at a nylon flocking plant in Rhode Island developed interstitial lung disease of unknown cause. Similar clusters at the same company's Canadian plant were reported...
TL;DR: At peak exercise, the distinct qualitative perceptions of dyspnea in patients with ILD were attributed to differences in dynamic ventilatory mechancis, i.e., reduced inspiratory capacity, heightened Pes-to-tidal volume ratio, and tachypnea.
Abstract: We compared qualitative and quantitative aspects of perceived exertional dyspnea in patients with interstitial lung disease (ILD) and normal subjects and sought a physiological rationale for their ...
TL;DR: It is proposed that the overexpression of 5-LO and FLAP represents evidence for the participation of inflammation in the process of PPH vasculopathy or, alternatively, that the overabundance of the enzymes involved in generation of inflammatory mediators may themselves be related to vascular cell proliferation and cell growth.
Abstract: Inflammatory infiltrates and endothelial cell proliferation have been appreciated in plexiform and concentric lesions, which characterize the vascular remodeling in primary pulmonary hypertension (PPH). Leukotriene production by perivascular and alveolar macrophages relies on activation of 5-lipoxygenase (5-LO), with translocation of the enzyme to the nuclear membrane, and association with the 5-LO activating protein (FLAP). Using immunohistochemical staining, we localized and semi-quantitatively estimated the abundance of 5-LO and FLAP in lungs obtained from patients with PPH, patients with interstitial lung disease (ILD), and normal control subjects. Expression of 5-LO and FLAP was prominent in alveolar macrophages in both the normal and PPH lungs; however, alveolar macrophages were more frequently clustered in the vicinity of remodeled blood vessel in PPH. Medium- and small-size pulmonary arteries in PPH showed more abundant FLAP expression than in control and ILD lungs. 5-LO expression in small arteries in PPH was more intense than in control and ILD patients. Endothelial cells in plexiform and concentric lesions in PPH expressed both 5-LO and FLAP. In situ hybridization confirmed the presence of 5-LO transcripts in macrophages and endothelial cells of the remodeled vessels in PPH. We propose that the overexpression of 5-LO and FLAP represents evidence for the participation of inflammation in the process of PPH vasculopathy or, alternatively, that the overabundance of the enzymes involved in generation of inflammatory mediators may themselves be related to vascular cell proliferation and cell growth.
TL;DR: In immunocompetent patients, the "benefit" of open lung biopsy is relatively low, as therapy changes substantially after OLB, but mortality is high, and OLB should be reserved for patients in whom the diagnosis is likely to lead to a change in therapy.
TL;DR: Results indicate that antigen-specific CD8(+) T cell recognition of an alveolar epithelial "autoantigen" is, in and of itself, sufficient to trigger an inflammatory cascade that results in the histological and physiological manifestations of interstitial pneumonia.
Abstract: CD8 1 T cells infiltrate the lung in many clinical conditions, particularly in interstitial lung disease. The role(s) that CD8 1 T cells might be playing in the pathogenesis of in- flammatory lung disease is unclear at present, as is the di- rect contribution of CD8 1 T cell effector activities to lung injury. This report describes a transgenic model used to evaluate the impact, on respiratory structure and function, of CD8 1 T lymphocyte recognition of a target antigen ex- pressed endogenously in alveolar epithelial cells. We found that adoptive transfer of cloned CD8 1 cytotoxic T lympho- cytes (CTLs) specific for an alveolar neo-antigen (influenza hemagglutinin) leads to progressive lethal injury in trans- genic mice, which dramatically affects lung structure and function. Transgenic recipients of CD8 1 CTLs exhibited tachypnea and progressive weight loss, becoming moribund over a period of several days. Concomitantly, the animals developed a progressive interstitial pneumonitis character- ized initially by lymphocytic infiltration of alveolar walls and spaces, followed by an exuberant mononuclear cell in- filtration that correlated with restrictive pulmonary me- chanics and a progressive diffusion impairment. These re- sults indicate that antigen-specific CD8 1 T cell recognition of an alveolar epithelial "autoantigen" is, in and of itself, sufficient to trigger an inflammatory cascade that results in the histological and physiological manifestations of intersti- tial pneumonia. ( J. Clin. Invest. 1998. 102:1653—1661.) Key words: T lymphocyte ¥ alveolar cell ¥ interstitial pneumonia ¥ lung injury ¥ diffusion
Journal Article•
TL;DR: The results suggest that intermittent treatment with i.v. cyclophosphamide reduces the severity of dyspnea, but fails to improve FVC or DLCO, or cause resolution of radiologic abnormalities, in patients with SSc.
Abstract: OBJECTIVE Pulmonary fibrosis, a frequent manifestation of systemic sclerosis (SSc), is considered incurable. Our aim was to assess the effect of therapy with intravenous (i.v.) cyclophosphamide on the course of pulmonary fibrosis in patients with SSc. METHODS Five patients with SSc and clinical, laboratory, or radiographic findings of interstitial lung disease were treated with cyclophosphamide (1 g) administered i.v. monthly for 48 weeks. The dyspnea score, pulmonary function tests, arterial blood oxygen content, radiologic abnormalities, and bronchoalveolar lavage (BAL) fluid cellularity were determined before and after therapy. RESULTS The dyspnea score decreased by 42% after 48 weeks of therapy. Forced vital capacity (FVC, percentage of predicted) increased by 7%, and carbon monoxide diffusing capacity (DLCO) decreased by 12%, but these changes were not statistically significant. Arterial blood oxygenation remained unchanged. At baseline, high resolution computed tomography of the lungs showed honeycombing, reticulonodular, or ground glass patterns in each patient examined. These radiologic abnormalities did not improve during treatment. A marked decrease in BAL fluid cell number, but not in the percentage of neutrophils, was observed after therapy. Nausea and leukopenia were frequent but mild side effects. One patient developed hemorrhagic cystitis. CONCLUSION The results suggest that intermittent treatment with i.v. cyclophosphamide reduces the severity of dyspnea, but fails to improve FVC or DLCO, or cause resolution of radiologic abnormalities, in patients with SSc.
TL;DR: A systematic approach to the diagnosis of pediatric ILD is useful, and not all patients need lung biopsy for diagnosis, according to this descriptive, observational, prospective study.
Abstract: Objective. To evaluate the value of a systematic approach to the diagnosis of pediatric interstitial lung disease (ILD). Methods. In this descriptive, observational, prospective study, we evaluated 51 children presenting with ILD of unknown etiology during a 3-year period. Specific clinical information regarding history, physical examination, diagnostic evaluation, and final diagnosis was recorded on each patient. Results. A specific diagnosis was established by history and physical examination alone in 1 patient, noninvasive tests alone in 8 others, and invasive tests, including lung biopsy, in another 26. Of the remaining patients, 8 had a suggestivediagnosis, and 8 had no specific diagnosis. Conclusions. A systematic approach to the diagnosis of pediatric ILD is useful, and not all patients need lung biopsy for diagnosis.
TL;DR: HRCT shows significant pulmonary disease in children with systemic sclerosis, revealing abnormalities in 91% of patients, and should be suspected inChildren with scleroderma, even if the chest radiograph has normal findings.
Abstract: The purpose of this study was to determine the prevalence of interstitial lung disease and the severity of disease in children with systemic sclerosis using high-resolution CT (HRCT).Eleven children (mean age, 11 years) with scleroderma underwent HRCT, chest radiography, and pulmonary function testing. Eight of these 11 patients also underwent follow-up HRCT. HRCT studies were assessed by two observers for ground-glass attenuation, honeycombing, and other abnormalities. Profusion scores for ground-glass attenuation and honeycombing were determined by multiplying severity of disease by the percentage of lung involvement.Chest radiographs predicted interstitial lung disease in only two patients, whereas HRCT showed interstitial lung disease in eight patients (p = .05). On HRCT, ground-glass attenuation was found in eight patients (73%), honeycombing in five patients (45%), linear opacities in six patients (55%), and subpleural micronodules in seven patients (64%). By the end of the study, 10 patients (91%) ...
TL;DR: Paediatric cases of interstitial pneumonitis in children are reviewed to look at the spectrum of histological patterns found in this age group and to determine whether the classification of such cases in childhood is both appropriate and worthwhile.
Abstract: Aims: Interstitial pneumonitis in children is very rare and most cases have been classified according to their counterparts in adults, although the term ‘chronic pneumonitis of infancy’ has recently been proposed for a particular pattern of interstitial lung disease in infants. We reviewed our paediatric cases of interstitial pneumonitis, first, to look at the spectrum of histological patterns found in this age group and, second, to determine whether the classification of such cases in childhood is both appropriate and worthwhile.
Methods and results
Twenty-five of 38 open lung biopsies showed an overlapping spectrum of interstitial pneumonitis, including three cases that fulfilled the histological criteria for chronic pneumonitis of infancy. There were 11 cases of reactive pulmonary lymphoid hyperplasia (either lymphoid interstitial pneumonitis or follicular bronchiolitis), five of which were associated with abnormalities of the immune system. Four cases were classified as desquamative interstitial pneumonitis and the remaining seven cases were classified as non-specific interstitial pneumonitis. There were no cases with the histological features of usual interstitial pneumonitis. Most patients responded to steroids but tended to have a residual deficit in lung function. Mortality appeared to be associated with presentation at a young age.
Conclusion
Classification of interstitial pneumonitis according to their adult counterparts is appropriate for this younger age group and can provide valuable information for the clinician. The term ‘chronic pneumonitis of infancy’ refers to a specific histological pattern, but whether it represents a separate disease or a reflection of pulmonary immaturity remains to be proven.
Journal Article•
TL;DR: A 48-year-old man was admitted because of persistent dry cough for six months He had been a smoker for 25 years, averaging a pack a day, and demonstrated clubbing of the fingers Basilar fine crackles were observed in both lung fields Chest X-ray films on admission showed diffuse reticulonodular shadows Chest computed tomograms showed low-attenuation areas mainly in the center of the upper lung field, and ground-glass opacity, air bronchiolograms, and perivascular interstitial thickening of the peripheral vessels mostly in the lower field as discussed by the authors
Abstract: A 48-year-old man was admitted because of persistent dry cough for six months He had been a smoker for 25 years, averaging a pack a day, and demonstrated clubbing of the fingers Basilar fine crackles were observed in both lung fields Chest X-ray films on admission showed diffuse reticulonodular shadows Chest computed tomograms showed low-attenuation areas mainly in the center of the upper lung field, and ground-glass opacity, air bronchiolograms, and perivascular interstitial thickening of the peripheral vessels mostly in the lower field A Gascintigram disclosed mild accumulation in both lungs A transbronchial lung biopsy specimen did not reveal special features However, a biopsy specimen obtained by thoracoscopy showed evidence of respiratory bronchiolitis, with a mononuclear inflammatory process involving respiratory bronchioles and adjacent air space, associated with mild fibrous thickening of the peribronchiolar interstitium and surrounding alveoli septa These findings suggested that the patient had respiratory bronchiolitis-associated interstitial lung disease, the second case to be reported in Japan
TL;DR: Lung tissue from patients with the acute respiratory distress syndrome was examined during exudative through to fibroproliferative stages, finding increased numbers of myofibroblasts and procollagen type I producing cells were frequently found early in the course of ARDS.
Abstract: Background—Mast cells (MCs), which are a major source of cytokines and growth factors, have been implicated in various fibrotic disorders. To clarify the contribution of MCs to fibrogenesis, lung tissue from patients with the acute respiratory distress syndrome (ARDS) was examined during exudative through to fibroproliferative stages. Methods—Lung tissue was obtained from 17 patients with ARDS who had pathological features of the early exudative stage (n = 6) or the later reparative stages (n = 11), from four patients with idiopathic pulmonary fibrosis, and from three patients with normal lung tissue. Immunohistochemical localisation of tryptase (found in all human MCs), chymase (found in a subset of human MCs), AE-smooth muscle actin (identifies myofibroblasts), and procollagen type I was performed. Results—Normal lung tissue exhibited myofibroblast and procollagen type I immunolocalisation scores each of 10 and MC scores of>2. Eighty percent of lung tissue samples from the early exudative stage of ARDS exhibited increased numbers of myofibroblasts, 50% had increased numbers of procollagen type I producing cells, while only 17% had increased numbers of MCs compared with control samples. All samples from the later reparative stages of ARDS had increased numbers of myofibroblasts and procollagen type I producing cells. Increased numbers of MCs were seen in 55% of samples from the reparative stages. There was no significant shift in MC phenotype in the ARDS samples. Conclusions—Increased numbers of myofibroblasts and procollagen type I producing cells were frequently found early in the course of ARDS. MC hyperplasia was unusual during this stage, but was often a feature of the later reparative stages. MCs do not appear to initiate fibroproliferation in ARDS. (Thorax 1998;53:823‐829)
TL;DR: Oedema formation in COPD is not cardiac in origin: in most patients, even when they are frankly oedematous, cardiac output is adequate for the body’s metabolic demands unless there is significant co-existent cardiac disease.
Abstract: Renal and hormonal abnormalities, usually manifested as oedema or hyponatraemia, are encountered frequently in patients with chronic obstructive pulmonary disease (COPD). The exact incidence of clinically significant oedema and hyponatraemia has not been documented. In advanced disease some degree of oedema is observed in a large proportion of patients; the pattern of hyponatraemia parallels that of oedema, but with a lower frequency. In the past, oedema in patients with COPD has been attributed to “cor pulmonale with backward heart failure”—that is, pulmonary hypertension induced by hypoxia and by structural changes in pulmonary arteries, increased systemic venous pressure, and reduced cardiac output. The onset of oedema is a poor prognostic factor; Renzetti and coworkers1 reported a four year mortality rate of 73% in patients with cor pulmonale compared with 53% for the whole group. Whether this reflects the advanced stage of the disease, the indirect effect of chronic diuretic therapy, or some undetermined insult on the function of critical organs is unclear. What is clear is that oedema formation in COPD is not cardiac in origin: in most patients, even when they are frankly oedematous, cardiac output is adequate for the body’s metabolic demands2 3 unless there is significant co-existent cardiac disease.
In 1960 Campbell and Short4 pointed out that, in patients with COPD, oedema is almost invariably associated with carbon dioxide (CO2) retention. They concluded that, in hypoxaemic normocapnic patients with chronic diffuse lung disease such as pulmonary fibrosis, oedema is uncommon and, in this setting, transient worsening in blood gas tensions during exercise or sleep, for example, should be suspected and ruled out. Since then sodium (Na+) retention in COPD has been considered to be the result of electrochemical imbalance (enhanced renal tubular H+/Na+ exchange with attendant increase in Na+ …
TL;DR: Lung transplantation is a viable option for patients with end stage pulmonary sarcoidosis and the medium term results are comparable with patients undergoing lung transplantation for other indications.
Abstract: Background—Lung transplantation is an accepted therapeutic option for patients with end stage pulmonary sarcoidosis. However, the medium term outcome of transplantation in this patient group is unknown. Methods—This study was performed to evaluate our experience with lung transplantation for end stage pulmonary sarcoidosis. Between July 1988 and July 1997 12 patients (nine men) underwent lung transplantation for sarcoidosis at our institution. Ten underwent single lung transplantation and two double lung transplantation. Results—Survival at three and five years was 70% and 56%, respectively. Three patients developed obliterative bronchiolitis at six,18,and 45 months.One died at the time of retransplantation. Sarcoid granulomas have recurred in the donor organ in three patients. In one the development of granulomas has been associated with clinical deterioration, necessitating retransplantation. Mean (SD) forced expiratory volumes in one second at three and five years were 1.37 (0.67) l and 1.34 (0.13) l, respectively. Conclusions—Lung transplantation is a viable option for patients with end stage pulmonary sarcoidosis.The medium term results are comparable with patients undergoing lung transplantation for other indications. Despite histological recurrence of sarcoidosis, the risk of clinically important recurrence is low. (Thorax 1998;53:281‐284)
TL;DR: Erythromycin exhibits a prophylactic effect on acute lung injury induced by intratracheal administration of bleomycin, which is possibly associated with a downregulation of neutrophil-derived elastase.
Abstract: BACKGROUND—Erythromycin has been reported to have an inhibitory effect on chronic inflammatory airway disease and chronic infiltration of neutrophils into the airway. Bleomycin (BLM) often induces interstitial lung fibrosis following acute lung injury. A study was undertaken to investigate the effects of erythromycin (EM) on experimental bleomycin-induced acute lung injury in rats.
METHODS—Bleomycin-induced lung injury was assessed by light microscopic examination, measurement of neutrophil elastase activity and of the interleukin 8 (IL-8) content in bronchoalveolar lavage (BAL) fluid. The potential inhibitory effect of erythromycin was assessed by overall comparison of erythromycin untreated (BLM alone), concurrently treated (BLM + EM), and pretreated (BLM +pre-EM) groups.
RESULTS—The neutrophil count and concentration of neutrophil-derived elastase in BAL fluid were significantly different in the three groups. The morphological changes of lung injury were also less extensive in rats pretreated with erythromycin. However, these protective effects were not marked in the group concurrently treated with erythromycin. Moreover, the concentration of IL-8 in the BAL fluid tended to be less in the erythromycin treated groups; however, there were no significant differences between the bleomycin-treated groups.
CONCLUSION—Erythromycin exhibits a prophylactic effect on acute lung injury induced by intratracheal administration of bleomycin, which is possibly associated with a downregulation of neutrophil-derived elastase.
TL;DR: This review explores the impact of high resolution computed tomographic (CT) scanning on the diagnosis and management of CFA.
Abstract: Despite recent technological advances, agreement amongst clinicians on an algorithm for the optimal management of cryptogenic fibrosing alveolitis (CFA) has proved to be elusive. The non-invasive diagnosis of CFA is often uncertain as the clinical features may mimic those of other interstitial lung diseases. Even when the diagnosis is secure, therapeutic decisions are not straightforward. Reversible inflammatory disease requires aggressive treatment, but side effects from an over-vigorous approach to irreversible fibrotic disease need to be avoided. The extent of disease may influence the approach to treatment, but the optimal means of staging initial severity remains contentious. Furthermore, precision in monitoring changes in disease severity at follow up is unattainable in some cases and this complicates therapeutic decisions. This review explores the impact of high resolution computed tomographic (CT) scanning on the diagnosis and management of CFA.
The integration of a new test into routine management is the product of rigorous initial assessment and subsequent accumulated clinical experience. Enduring changes in clinical practice seldom result solely from “landmark” series. For example, early reports suggested that bronchoalveolar lavage (BAL) might offer invaluable additional diagnostic and prognostic information in diffuse lung disease.1 2 However, subsequent clinical experience has shown that diagnostic and prognostic trends obtained fron BAL in groups of patients are not sufficiently robust to change management substantially in most cases.3 In the same way, although disease activity defined by 67-gallium scanning was shown to correlate with inflammatory cell content on open lung biopsy material,4 it transpired that 67-gallium scanning did not predict responsiveness to treatment.5 Initial enthusiasm generated by early studies of diagnostic tests followed by disappointment is a familiar cycle for clinicians managing patients with interstitial lung disease.
Will this sequence of events apply equally to the use of CT scanning in the management of CFA? …
TL;DR: It can be speculated that the response to intermittent high‐dose intravenous methylprednisolone may explain the ability of this mode of hormone administration to maintain an adequate level of glucocorticoid receptor expression.
Abstract: The prognosis for children with chronic interstitial lung disease is poor and the mortality rate is high, especially in infants. This explains the many therapeutical protocols which have been proposed and investigated by several authors. In the present work, we evaluated the response of three infants with idiopathic pulmonary fibrosis to high-dose intravenous prednisolone pulses. The patients were referred to the department at the age of 4, 17, and 3 months, respectively. The diagnosis was confirmed by open lung biopsy and intravenous pulse methyl prednisolone therapy was started with the following protocol: 300 mg/m2 methylprednisolone daily for 3 days, repeated every 4 to 6 weeks. Because of the extreme severity of the respiratory distress at the time of diagnosis, the intravenous pulse treatments were initially complemented by oral prednisone. Clinical improvement was noticed within 6 months with progressive correction of hypoxemia. After follow-up for 3.5 to 4 years, with a total number of pulses of 37, 26, and 32, respectively, the children are symptom-free and do not require oxygen supplementation. During this period, no side effects and no adrenal insufficiency could be documented. Based on current knowledge of steroid action, it can be speculated that the response to intermittent high-dose intravenous methylprednisolone may explain the ability of this mode of hormone administration to maintain an adequate level of glucocorticoid receptor expression. More information and trials through multicenter collaborations are needed to assess therapeutical protocols of repeated high-dose intravenous steroid treatment.
TL;DR: Although the clinical significance and pathogenesis of osteoporosis in AS remain unclear, reduced bone mass may be found in a significant number of patients and this area of future research is the detection of both disease-related variables and sociomedical factors influencing the final outcome of this disease.
Abstract: Ankylosing spondylitis (AS) almost invariably starts before the age of 50, and clinical features suggestive of AS in older age should lead to consideration of other rheumatic disorders. Clinical manifestations of extraskeletal tissue such as renal amyloidosis and lung disease may occur. However, the detection of amyloidosis may not invariably infer poor prognosis, and associated lung disease may include apical fibrosis and also interstitial lung disease. Although the clinical significance and pathogenesis of osteoporosis in AS remain unclear, reduced bone mass may be found in a significant number of patients. Population surveys on AS have shown a correlation between the population frequency of HLA B27 and prevalence of AS. However, neither B27 subgroup distribution nor low frequency of B27 can explain the rarity of AS among certain African regions. Also representing an area of future research is the detection of both disease-related variables and sociomedical factors influencing the final outcome of this disease.
TL;DR: Cardiopulmonary exercise testing can elucidate the relative contributions of these mechanisms and guide therapy in ILD, and functional CT imaging may provide insight into the relationship between structural and physiologic abnormalities of regional pulmonary function.
Abstract: Interstitial lung disease (ILD) limits exercise capacity through a variety of complex and intriguing mechanisms, including ventilatory limitation, diffusion impairment, and ventilation-perfusion derangement. Resting pulmonary function testing seldom explains the symptoms nor defines the specific pathophysiology of the individual patient. Cardiopulmonary exercise testing can elucidate the relative contributions of these mechanisms and guide therapy. A fundamental problem in ILD is one of inadequate time for lung inflation during intense exercise, resulting in dynamic hypoinflation relative to the ventilatory demand. Pulmonary rehabilitation is underused in ILD. Functional CT imaging may provide insight into the relationship between structural and physiologic abnormalities of regional pulmonary function. Recent advances in nitric oxide research will perhaps further our understanding of the basic pathophysiology of ILD and provide specific treatment for the associated pulmonary vascular disease.