Fibrosing alveolitis

Fibrosing alveolitis is a disease of unknown cause mainly involving the gas-exchanging portions of the lungs. It may occur in isolation and be called cryptogenic or idiopathic, in which case the clinical manifestations are mainly respiratory, or it may be associated with other disorders, such as rheumatoid arthritis. The histopathologic abnormalities of the pulmonary tissue are identical in either instance. Other names used for the disease have included usual interstitial pneumonia, desquamative interstitial pneumonia and the Hamman-Rich syndrome; these terms may describe different stages of the same pathologic process. Many authors in North America and those in the United Kingdom favour the term fibrosing alveolitis when describing chronic interstitial pneumonias. There may be accompanying nonspecific Immunologic abnormalities, which may denote that fibrosing alveolitis is part of the wide spectrum of diseases known as connective tissue disorders. Recently immune complexes have been found in the lung parenchyma; they probably result in the granulocyte destruction and reticuloendothelial proliferation seen in the acute phase of the disease.There are no specific diagnostic tests for the disease apart from lung biopsy, which can be performed at the time of thoracotomy or transbronchially, with the use of a flexible fibreoptic bronchoscope. Lavaged cells from the alveoli have also been obtained via the bronchoscope; in persons with fibrosing alveolitis a high proportion of these cells are neutrophils, and after corticosteroid treatment the proportion decreases. The progress of the disease can be followed by examination of these washings as well as by lung scanning with gallium-67 citrate. Newer methods of treatment using combinations of corticosteroids and immunosuppressant drugs are being evaluated and are initially proving to be successful.     

Autoantibodies in cryptogenic fibrosing alveolitis

The pathogenesis of cryptogenic fibrosing alveolitis (CFA) involves injury, an immune/inflammatory response and fibrosis. The cause of the injury is unknown, but the identification of serum autoantibodies makes an autoimmune aetiology attractive. The core study on which this commentary is based used novel cloning and serum screening technologies in order to identify new public and private autoantibodies in sera from 12 patients with CFA. Largely negative conclusions were drawn from that study. However, we suggest that the prevalence of autoantibodies may have been underestimated, that the study was timely and that this approach is worth pursuing further.     

Rising mortality from cryptogenic fibrosing alveolitis.

OBJECTIVE--To determine the pattern of mortality ascribed to cryptogenic fibrosing alveolitis and to identify factors that might be important in the aetiology of the disease; and to assess the validity of death certification of the disease. DESIGN--A retrospective examination of mortality ascribed to cryptogenic fibrosing alveolitis in England and Wales between 1979 and 1988 with analysis, by multiple logistic regression, of independent effects of age, sex, region of residence, and social class as indicated by occupation on data for 1979-87; also a retrospective review of hospital records of patients certified as having died of cryptogenic fibrosing alveolitis in Nottingham and of the certified cause of death of patients known to have had the disease. MAIN OUTCOME MEASURES--Time trends in mortality nationally; effects on mortality of age, sex, and region of residence; validity of death certification in Nottingham. RESULTS--The annual number of deaths ascribed to cryptogenic fibrosing alveolitis doubled from 336 in 1979 to 702 in 1988, the increase occurring mainly at ages over 65. Mortality standardised for age for both sexes likewise increased steadily over the period. Deaths due to cryptogenic fibrosing alveolitis were commoner in men (odds ratio 2.24, 95% confidence interval 2.11 to 2.33) and increased substantially with age, being 7.84 (7.24 to 8.49) times higher in subjects aged much greater than 75 than those aged 45-64. Odds ratios of death due to cryptogenic fibrosing alveolitis adjusted for age and sex were increased in the traditionally industrialised central areas of England and Wales (p less than 0.02, maximum odds ratio between regions 1.25), but no significant increase in odds of death was found for manual occupations. Of 23 people whose deaths were registered in Nottingham as having been due to cryptogenic fibrosing alveolitis, 19 were ascertained from clinical records to have had the disease. Only 17 of 45 patients known to have had cryptogenic fibrosing alveolitis in life were recorded as having died from the disease. CONCLUSIONS--The diagnostic accuracy of death certification of cryptogenic fibrosing alveolitis is high, but the number of deaths recorded as being due to the disease may underestimate the number of patients dying with the disease by up to half. Mortality due to the disease is increasing, and the male predominance and regional differences in mortality suggest that environmental factors are important in its aetiology.     

Extrinsic allergic alveolitis

Extrinsic allergic alveolitis is caused by the inhalation of small organic allergen particles by non-atopic subjects which provoke an allergic reaction, thought to be chiefly due to a type III mechanism, in the peripheral respiratory tissues. The clinical features are determined by the nature of exposure, the immunopathological mechanism(s) involved and the site of reaction in the lung. When the exposure is intermittent and intensive, febrile episodes with respiratory symptoms beginning after four to six hours are prominent, but when it is more continuous and less intensive they are not and the features are those of a chronic fibrosing lung disease. The diagnosis is important to make because management by the avoidance of exposure is followed by improvement. It is made by recognizing the clinical presentation, by identifying the source of allergen exposure and by obtaining supportive evidence from precipitin and skin tests, or from allergen inhalation tests or lung biopsy.     

Respiratory syndrome very similar to extrinsic allergic alveolitis due to Penicillium verrucosum in workers in a cheese factory

A respiratory syndrome very similar to extrinsic allergic alveolitis due to Penicillium verrucosum was recognized in 4 workers employed in a Gorgonzola cheese factory. A mycogen allergy to P. verrucosum, used as starter in the production, was demonstrated by positive sputum culture and detection of specific antibodies in the blood. Intense and prolonged exposure to inhalation of fungal spores could have lead to the development of this allergic response. The fact that 2 of the subjects are siblings seems to indicate host susceptibility or immunological constitution in the pathogenesis of the respiratory allergy. This revised version was published online in June 2006 with corrections to the Cover Date.     

Specific features of humoral immunity in cryptogenic fibrosing alveolitis patients

Cryptogenic fibrosing alveolitis (CFA) is a severe autoimmune disease of unclear etiology and prognostically unfavorable. The complexity of the diagnostics of this disease makes it necessary to search for new methods; for this reason immunity in CFA patients must be studied. The study of humoral organ-specific, organ-unspecific and antibacterial immunity of CFA patients revealed that the latter differed from the members of the groups used for comparison by a higher frequency of positive reactions in EIA determinations of IgG antibodies to cytokeratin-8 and Moraxella catarrhalis antigens. In addition, only in CFA patients a high degree of correlation (r=0.88) between these results was established. This made it possible to propose to use these reactions for confirming the diagnosis of CFA and suggested the probable role of M. catarrhalis in triggering autoimmune reactions characteristic of this disease.     

Primary chylopericardium associated with allergic alveolitis.

A 42-year-old woman with extrinsic allergic alveolitis and worsening dyspnea was found to have an enlarged cardiac silhouette. Primary chylopericardium was diagnosed when pericardiocentesis yielded the characteristic milky-white fluid containing microscopic fat droplets. The pericardial effusion resolved with prednisone therapy.     

BN 52021 (a platelet activating factor-receptor antagonist) decreases alveolar macrophage-mediated lung injury in experimental extrinsic allergic alveolitis.

Several lines of research indirectly suggest that platelet activating factor (PAF) may intervene in the pathogenesis of extrinsic allergic alveolitis (EAA). The specific aim of our study was to evaluate the participation of PAF on macrophage activation during the acute phase of EAA in an experimental model of this disease developed in guinea pigs. Initially we measured the concentration of PAF in bronchoalvedar lavage fluid, blood and lung tissue. In a second phase we evaluate the participation of PAF on alveolar macrophage activation and parenchymal lung injury. The effect of PAF on parenchymal lung injury was evaluated by measuring several lung parenchymatous lesion indices (lung index, bronchoalvedar lavage fluid (BALF) lactic hydrogenase activity and BALF alkaline phosphatase activity) and parameters of systemic response to the challenge (acute phase reagents). We observed that induction of the experimental EAA gave rise to an increase in the concentration of PAF in blood and in lung tissue. The use of the PAF-receptor antagonist BN52021 decreases the release of lysosomal enzymes (beta-glucuronidase and tartrate-sensitive acid phosphatase) to the extracellular environment both in vivo and in vitro. Furthermore, antagonism of the PAF receptors notably decreases pulmonary parenchymatous lesion. These data suggest that lung lesions from acute EAA are partly mediated by local production of PAF.     

Budgerigar-fancier's lung: the commonest variety of allergic alveolitis in Britain.

A questionnaire survey of 1005 consecutive attenders at four outpatient clinics yielded 117 (12%) budgerigar fanciers (exposed to budgerigars- known in North America as parakeets-for at least three months) and 296 (29%) former fanciers. Twnety had precipitins to budgerigar serum or droppings or both, and 10 of these together with 39 precipitin-negative patients reported undue breathlessness on exertion during exposure to buderigars. These 59 patients were investigated further, seven completing a series of inhalation provocation tests with budgerigar antigens designed to confirm or exclude budgerigar-fancier''s lung (BrFL). Typical positive responses were obtained from four current and one former fancier. The prevalence of confirmed BrFL among the 11n current budgerigar fanciers was 3.4% (four cases). This was biased, however, by the inclusion of one patient whose attendance at the surveyed clinic was attributable to the disease. With the exclusion of this patient, confidence limits suggested that the true prevalence of BrFL among current budgerigar fanciers in the general population lies between 0.5% and 7.5%, which is similar to the prevalence of farmer''s lung in farm workers. In view of the enormous population at risk, however, this implies that BrFL rather than farmer''s lung is by far the commonest type of allergic alveolitis in Britain.     

Private specificities can dominate the humoral response to self-antigens in patients with cryptogenic fibrosing alveolitis

Background  

The pathogenetic mechanisms that underlie the interstitial lung disease cryptogenic fibrosing alveolitis (CFA) may involve an immunological reaction to unidentified antigens in the lung, resulting in tissue damage.     

Production of H2O2 by alveolar macrophages in experimental allergic alveolitis

Experimental extrinsic allergic alveolitis (EAA) was induced in guinea pigs with Saccharopolyspora rectivirgula. Bronchoalveolar lavages were performed before inducing EAA (day 1, BAL 1), on day 23 (BAL 2), and on day 48 (BAL 3). The number of cells/ml in lavage fluid was increased at BAL 2 (4.79 x 10(6) and BAL 3 (4.29 x 10(6)) compared with BAL 1 (0.56 x 10(6)). The number of major cell types increased simultaneously, neutrophil becoming the predominant cell type over alveolar macrophages (AM). The production of H2O2 by AM was measured at the different phases of EAA. Adherent AM were either non-stimulated or triggered with phorbol myristate acetate (PMA), zymosan. S. rectivirgula opsonized with normal guinea pig serum (SRNS), or S. rectivirgula opsonized with guinea pig anti-S, rectivirgula serum (SRAS). Stimulated AM produced larger quantities of H2O2 than unstimulated cells, PMA being the most potent stimulus. At day 1, AM stimulated with S. rectivirgula and zymosan produced similar quantities of H2O2. After the induction of the disease, AM stimulated with S. rectivirgula produced larger quantities of H2O2 than with zymosan. Production of H2O2 by AM stimulated with S. rectivirgula or PMA, respectively, stayed the same at day 1 and 23, but increased sharply for both stimuli at day 48. There was no difference between H2O2 production by AM triggered with SRNS or with SRAS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exhaled breath profiling by electronic nose enabled discrimination of allergic rhinitis and extrinsic asthma

Aim: To assess whether an e-nose could discriminate between subjects affected by allergic rhinitis with and without concomitant extrinsic asthma, as well as from healthy controls, in terms of exhaled VOC-profile.

Methods: Fourteen patients with Extrinsic Asthma and Allergic Rhinitis (AAR), 14 patients with Allergic Rhinitis without asthma (AR) and 14 healthy controls (HC) participated in a cross-sectional study. Exhaled breath was collected by a standardized method and sampled by an e-nose (Cyranose 320). Raw data were reduced by Principal component analysis and analyzed by canonical discriminant analysis. Cross-validation accuracy (CVA) and Receiver Operating Characteristic(ROC)-curves were calculated. External validation in newly recruited patients (7 AAR, 7?AR and 7 HC) was tested using the previous training model.

Results: Breathprints of patients with AR clustered from those with AAR (CVA?=?85.7%), as well as HC (CVA?=?82.1%). Breathprints from AAR were also separated from those of HC (CVA?=?75.0%). External validation confirmed the above findings.

Conclusions: An e-nose can discriminate exhaled breath from subjects with allergic rhinitis with and without extrinsic asthma, which represent two different diseases with partly overlapping features. This supports the view of using breath profiling to diagnose asthma also in patients with allergic rhinitis.     

The modifications produced in allergic alveolitis and in Goodpasture's syndrome due to exposure to cigarette smoke.

Two groups of rats with experimental alveolitis were exposed to cigarette smoke. After comparing the results, the possible muffling effect of the cigarette smoke related to interstitial lung disease was discussed. 180 rats were divided into 6 groups of 30 animals each: Group 1: untreated controls; Group 2: exposed to cigarette smoke for 2 months; Group 3: sensitized with bovine albumin (BA) and exposed to an atmosphere with this antigen for two months, to reproduce a type of extrinsic allergic alveolitis (EAA); Group 4: treated with a single daily dose of anti-lung serum for three days followed by two days without treatment, to reproduce a type of Goodpasture's syndrome; Group 5: exposed to cigarette smoke and to BA; Group 6: exposed to cigarette smoke and treated with anti-lung serum. The animals were sacrificed and their lungs were treated for: Bronchoalveolar lavage (BAL), percentage lymphocyte count, polymorphonuclear (PMN) and alveolar macrophages (AM); semiquantitative and morphometric histological study. The semiquantitative study determined the area of the studied lung incision, affected by granulomae, increased alveolar aerial spaces, thickened alveolar walls and haemosiderine lung area. The morphometric study, based on the linear integration method, evaluated: the distance between two alveolar walls, the amount of interstice per field; and the number of AM with haemosiderine per field was counted. From the results we point out that the treated animals had significantly higher lymphocyte and BAL PMN counts than the untreated ones; no significant differences were found between the singly and doubly treated animals. The animals exposed to cigarette smoke and treated with anti-lung serum were those that showed the least number of lymphocytes and PMN of all the treated animals. The semiquantitative variables studied were all increased in comparison to the control group, most of the increases being significant. The morphometric variables revealed significant differences with respect to the untreated group, except for the animals which were treated with anti-lung serum and cigarette smoke, which showed a minimum decrease in the alveolar size and a slight increase of the interstitial tissue. Only one morphometric variable showed a significant difference between the group treated with anti-lung serum and the one treated with anti-lung serum and cigarette smoke: the number of AM with haemosiderine in the lung.(ABSTRACT TRUNCATED AT 400 WORDS)     

A comparative evaluation of the results of classical x-ray study and computed tomography in patients with exogenous allergic alveolitis

A correlative study of the results of x-ray investigation using routine methods and computerized tomography (CT) was conducted to specify the roentgenomorphological substrate of changes in patients with exogenous allergic alveolitis. The established complex of routine methods is informative enough to interpret the revealed changes. However, at early stages CT helps to specify semiotics and permits obtaining additional information, particularly on quantitative, i.e. densitometric changes. In diffuse and disseminated pulmonary lesions CT can be used as an additional method.