Effect of short-term, low-level nitrogen dioxide exposure on bronchial sensitivity of asthmatic patients.

Our purpose was to determine whether exposure to a realistic concentration of nitrogen dioxide (NO2) could increase the bronchial sensitivity of asthmatic patients to bronchoconstrictor agents. We established dose-response curves for changes in specific airway resistance (SRaw) in response to aerosolized carbachol in 20 asthmatics after each had spent 1 h in an exposure chamber breathing on one occasion unpolluted air and on a separate occasion 0.1 ppm NO2: sequence of exposures to unpolluted air and to low levels of NO2 were randomized in a single-blind fashion. NO2 induced a slight but significant increase in initial SRaw and enhanced the bronchoconstrictor effect of carbachol in 13 subjects: curves were shifted to the left and the mean dose of carbachol producing a twofold increase in initial SRaw was decreased from 0.66 mg to 0.36 mg (P less than 0.001). In contrast, NO2 neither modified the initial SRaw nor the bronchoconstrictor effect of carbachol in seven subjects. In 4 out of the 20 subjects, exposure to a higher concentration of NO2 (0.2 ppm) yielded variable results. Potentiation of the carbachol bronchoconstrictor response by NO2 could not be related to any physical or clinical characteristics of the subjects tested. Although the mechanisms underlying the NO2 effect remain controversial, the present results demonstrate that very low levels of NO2 can adversely affect some asthmatics.

Spin coating of non-Newtonian fluids with a moving front.

We investigate axisymmetric spin coating of power law and Ellis fluids. The flow is driven by centrifugal force, gravity and surface tension. For power law and Ellis models a single equation for the fluid film height is obtained. For a Newtonian fluid the flux only involves linear derivative terms which allows the flux to be easily split for a numerical scheme. For power law and Ellis models the derivatives appear as nonlinear terms. To overcome this we develop an alternative numerical scheme to solve for the film height. Neglecting surface tension and gravity the power law model shows a central spike which is reduced by the introduction of surface tension and gravity. In certain cases the shear thinning power law model predicts slower spreading than the Newtonian model. The Ellis fluid shows no central spike, even for zero surface tension and the film always spreads further than the Newtonian fluid.

What can be measured with RAST?

A theoretical study of the basic principles involved in Radioallergosorbent test (RAST) showed that: 1) When a given serum is tested, the significance of the numerical value obtained with RAST depends upon the serum assayed and the allergosorbent preparation, in a rather unpredictable way. Three factors can be measured: a) The percentage of specific IgE antibodies among all allergen-specific antibodies; b) The specific IgE antibody level; c) The product of the specific IgE antibody level and its affinity constant. 2) Simple graphical techniques allow a straightforward determination of all these factors if four dilutions of each serum are assayed at the same time. The results are expressed in two constant parameters (arbitrary IgE unit and allergosorbent capacity). It is concluded that these theoretical calculations may give a fair account of a lack of correlation between specific IgE antibody levels (as assayed with RAST) and several clinical and biological parameters. Furthermore, they provide a simple procedure which makes such tedious manipulations as specific IgE antibody purification quite necessary.

Increased endothelin-1 associated with bacterial infection in lung transplant recipients.

BACKGROUND: Endothelin-1 (ET-1) has fibrogenic and inflammatory properties. Its pathogenic role in pulmonary fibrosis and certain inflammatory airway diseases is now well known. Its production is, in part, triggered by infectious processes. Episodes of infection are suspected to be involved in the development of bronchiolitis obliterans syndrome (BOS), which is the main feature of chronic lung rejection and the major factor limiting the long-term survival of transplanted patients. We postulated that ET-1 is upregulated during infectious complications arising from the graft and that this could partly explain the remodeling of airway structures observed in BOS. We, therefore, set up this study to assess ET-1 expression in relation to complications of the graft in human lung transplant recipients. METHODS: ET-1 mRNA was quantified by reverse transcription-competitive polymerase chain reaction in cells from 119 samples of bronchoalveolar lavage (BAL) fluid from 17 lung transplant recipients. ET-1 and big ET-1 proteins were assessed in BAL cell culture supernatants by enzyme immunoassay. Transbronchial biopsies (n=21) were stained immunohistochemically for ET-1 receptors. RESULTS: Episodes of bacterial infection strongly correlated with increased ET-1 mRNA and protein expression. ET-1 receptors were also upregulated during these episodes, especially on endothelial and smooth muscle cells. Five of the seven patients with the highest ET-1 levels subsequently developed BOS. CONCLUSIONS: These results raise the possibility that ET-1, part of whose production is triggered by infectious postgraft complications, might play a role in the development of BOS through its potential effects on airway remodeling.

Peaks of transforming growth factor-beta mRNA in alveolar cells of lung transplant recipients as an early marker of chronic rejection.

BACKGROUND: Chronic lung rejection (CLR) induces a fibroproliferative disorder leading to the occlusion of small airways. It has emerged as the major factor limiting the survival of lung transplant recipients. Predictive markers of CLR are lacking, and its diagnosis is generally ascertained when the fibrosis process is irreversible. METHODS: We have quantified the expression of transforming growth factor-beta (TGF-beta), a critical mediator of fibrogenesis, in alveolar cells from lung transplant recipients using a competitive reverse transcriptase polymerase chain reaction method. RESULTS: We have shown that patients with CLR presented marked peaks of TGF-beta mRNA expression, in contrast with patients without CLR. These peaks preceded the diagnosis of CLR by several months in two of three patients who died within 2 years of diagnosis. CONCLUSIONS: Our data suggest that TGF-beta expression in alveolar cells could serve as an early predictive and prognostic marker of chronic lung rejection.

Asthma and allergy to house-dust mites in populations living in high altitudes.

Do subjects living in high altitude where house-dust mites are known to be uncommon exhibit a lower prevalence of asthma and allergy to house-dust mites? To answer this question, we compared the prevalence rates of asthma and skin reactions to house-dust mites in two towns with contrasted environments: Marseille, located on the seashore, and Briançon, 1350 m in altitude. The study population consisted of a random sample of 4,008 people in Marseille and 1,055 people in Briançon. All subjects received a home questionnaire, and a sample of patients and asymptomatic subjects had a skin-prick test evaluation. The cumulative prevalence of asthma was equal to 4.1 percent in Marseille and 2.4 percent in Briançon, a difference which was significant (p = 0.01). The prevalence of positive skin tests to housedust mites in asymptomatic subjects was equal to 27.5 percent in Marseille and 10.2 percent in Briançon (p less than 0.001). This study supports the hypothesis that exposure to environmental factors may have a major influence on developing allergic diseases.

Histamine release reaction of basophils in chronic granulocytic leukaemia. Induction by heterologous anti-immunoglobulin E, concanavaline A, and phytohaemagglutinin; effect of heavy water.

Basophils possess membrane bound IgE molecules, and immunological activation leads to a secretory process with cell degranulation and histamine release. Heterologous anti IgE, concanavaline A, and phytohaemagglutinin are potent non-cytotoxic releasing agents. They operate by a mechanism similar to that of immunological activation. Heavy water is not a histamine releasing inducer but it increases histamine release of the cells. We studied the histamine release reaction of leukaemic basophils in 10 patients and found a physiological response such as that previously reported with normal human basophils.

In vitro evaluation of blocking antibodies by RAST interference during pollen desensitization: role of the IgG fraction.

RAST interference was used to study the changes in blocking antibodies during hyposensitization. At the onset of desensitization blocking antibodies levels were correlated to IgE antibody titers. They progressively rose during the treatment. IgG isolated by adsorption onto protein A Sepharose were only a part of blocking antibodies. The isolated antibodies gave 80% of RAST interference values. Results showed that RAST interference may be used routinely to determine changes of immunological parameters of immunotherapy.

French multicentre double-blind study to evaluate the efficacy and safety of acrivastine as compared with terfenadine in seasonal allergic rhinitis.

In this double-blind, multicentre study the antihistamine acrivastine was compared with terfenadine for the treatment of seasonal allergic rhinitis. The study was divided into three periods which together lasted 56 days. Patients (n = 83) were randomly assigned treatment with either 8 mg acrivastine three times daily or 60 mg terfenadine twice daily. Both agents were equally efficacious in reducing the severity of sneezing, itchy nose, blocked nose, running nose, itchy eyes, watery eyes and itchy throat as recorded daily by patients, and as rated by both the patients and their physicians at the end of each treatment period. Acrivastine and terfenadine were equally well tolerated with no serious side-effects. Both effectively controlled the symptoms of seasonal allergic rhinitis in otherwise healthy individuals.

[Asthma and pollens]. / Asthme et pollens.

Hay fever was well described by Blackley in 1973. The frequency of pollen asthma may be expressed as a percentage of general frequency of hay fever. The figure of Hagy and Settipane of 21% for students with a mean age of 17.9 years is quoted and ended with different results to the french study by Denis and Perdrizet of 6.5% in students with a mean age of 23 years. One may also express the frequency of asthma in subjects suffering from hay fever which vary greatly with the different plant families. The seasonal rhythm and the oculo-nasal accompaniment are very characteristic. The clinical "scores" of patients have been analysed in parallel with the atmospheric curves of pollen gathered. The current problems of hay fever are particularly: The problem of the penetration of the antigen into the bronchi, the methods of study are reviewed. Little pollen reaches the bronchi. In order to explain this paradox of pollen asthma vagal reflexes from the pharynx are involved and a possible penetration to the bronchi of fragments of pollen and above all aerosols containing allergens (Solomon). Why is it that certain patients have asthma and others only coryza? Perhaps the bronchial reaction is linked to different dose of antigen, to nasal obstruction which makes the subject breath with an open mouth, to different immunological phenomena more intensive in asthmatics than in the subject suffering from coryza (Kaliner) and the bronchial reactivity of certain subjects. In an inverse sense the allergy provokes or increased bronchial reactivity. Finally the early and delayed allergic responses to pollen are a model of what is an oedematous reaginic reaction then inflammatory.

[Epidemiological approach to the relationship between bronchiectasis and sterility]. / Approche épidémiologique de la relation bronchectasies-stérilité.

In recent years associations have been reported between male infertility and chronic pulmonary infections. These disorders include immotile-cilia syndrome, cystic fibrosis and Young's syndrome. For each disorder, case reports or small groups of patients have been described. However, it remains to be determined if these congenital disorders play a significant role in primary bronchiectasis (P.B). To do this, we compared the fertility rate of 35 patients (24 males, 11 females) with clinical and radiological evidence of P.B. and of 71 patients (54 males, 17 females) with secondary bronchiectasis (S.B) due to a defined chest disease (mainly tuberculosis and chronic bronchitis with emphysema). We abstracted the clinical records of this group of 106 patients, hospitalized between 1966 and 1983 for: age at the time of hospitalization, sex, diagnosis (P.B. vs. S.B.), association with sinusitis and situs inversus, socio-economic status, ethnic group, marital status and fertility (graded as 0 or 1+). The crude association between P.B. and infertility is strong (p greater than 0.10). However age may represent a confounding factor as patients with P.B. are younger (p less than 0.01) than patients with S.B., and more often single (p less than 0.01). Initially we restricted the analysis to married patients of both groups, and still got a significant association. Then we compared mean age in childless married people of both groups and observed a non-significant difference. Moreover, when we compared fertility in older patients, for example in people over 30 years old, the association still persists (p less than 0.03). In conclusion, the congenital disorders associating bronchiectasia and infertility must be looked for in the check up of P.B., all the more so as some can be cured of their infertility.

[Suspicion on sulfites]. / Suspicion sur les sulfites.

The sulfites have anti-oxygen and anti-microbial properties, which explain their great use in the food and drug industry. They may be responsible for anaphylactoid type episodes or more often asthmatic crises. 4 to 8% of asthmatics are sensitive to sulfites. The majority of asthmatics who are sensitive to sulfites are steroid dependent asthmatics. The pathophysiology is not clear: either a reaginic mechanism, reflex bronchoconstriction to SO2, a partial deficit in sulfite-oxidases. The diagnosis rests on oral provocation tests. These tests should be carried out according to a rigorous methodology, because there are frequent false positives (57 to 70%). Tests of alimentary provocation do not always correlate with the results from oral provocation tests to sulfites and pose the double question of sensitivity to the combined forms of sulfites which are present in food, and the reality of the risk of exposure of asthmatics to these foods. The prevention of any such mishaps rests on the eviction of such substances from the food which is often difficult and also of drugs. Vitamin B12, atropine, doxepin and sodium cromoglycate are capable of preventing totally or partially the bronchospasm induced by the absorption of sulfites.

[Immediate hypersensitivity to quinine]. / Hypersensibilité immédiate à la quinine.

Systemic anaphylactic reaction with shock was observed after ingestion of an antipyretic combination product containing quinine. That quinine was responsible for the reaction was proven by immediate skin tests and by oral challenge tests. The demonstration of specific IgE's by a radioallergosorbent test (RAST) provided evidence for an immediate hypersensitivity mechanism.

[The role of alpha-amylase in baker's asthma]. / Rôle de l'alpha-amylase dans l'asthme du boulanger.

We report a case of asthma in a baker provoked by an additive which is generally used in bread making, namely alpha-amylase, an extract of Aspergillus oryzae. Skin tests to alpha-amylase were positive in a concentration of 0.1 micrograms/ml. Specific IgE was detected to this enzyme. A provocation test to alpha-amylase was positive with a fall of the FEV1 of 42%. Provocation tests to flour gave a negative immediate and delayed reaction. Progress was made towards the disappearance of symptoms after several months of avoiding the allergen. This observation has enabled us to show the specificity of the allergy to alpha-amylase, a glycolytic enzyme, coming in the group of occupational diseases n. 63 (asthma due to lyophilised enzymes) whereas baker's asthma is at n. 66.

[Prevention of infections in chronic bronchitis using vaccination and/or immunomodulation]. / Prévention des infections chez les bronchitiques chroniques par la vaccination et/ou l'immunomodulation.

Polyvalent antimicrobial vaccines have been widely used in chronic bronchitis for nearly fifty years without their effect or mechanism of action always being well understood. The polysaccharide vaccines, in particular pneumococcal, are better defined chemically and in their mode of action. However, it does not seem that ordinary chronic bronchitis is a good indication for these vaccines. The immunomodulators, extracts of the cell wall of certain bacteria, are aimed at increasing the host's defence capacity in a non-specific manner. The addition of ribosomes may favour specific and non-specific immunomodulation. Certain vaccines have shown their efficacy in reduction of infective episodes in chronic bronchitis. However, other studies ought to be undertaken to obtain purified products which are not toxic and are yet more effective. Finally, it is necessary to have better knowledge of the mode of administration and of the doses administered corresponding to the optimal efficacy of the vaccines.

[Use of azlocillin in the treatment of Pseudomonas bronchopulmonary infections]. / Utilisation de l'azlocilline dans le traitement des infections broncho-pulmonaires à Pseudomonas.

Eleven patients with severe bronchopulmonary infection due to Pseudomonas were treated with azlocillin in doses of 250 mg/kg/day. Severe preexisting respiratory diseases, such as bronchopulmonary carcinoma, bronchiectasis or respiratory insufficiency were present in all cases. All patients had been unsuccessfully treated with various antibiotics before they received azlocillin. The pathogenicity of the isolates was assessed by germ counts in sputum. Comparative in vitro sensitivities to carbenicillin and azlocillin were determined by the disc method and by measurement of the minimum inhibitory concentrations in liquid medium. All strains of Pseudomonas aeruginosa isolated were sensitive to azlocillin with minimum inhibitory concentrations of 0.5 to 64 micrograms/ml. When tested against carbenicillin, 4 of the strains were resistant and 1 had intermediate sensitivity. The carbenicillin/azlocillin minimum inhibitory concentrations ratio was usually equal to 4. Clinical results were satisfactory in 7 cases; inadequate response or failure was observed in 4 cases and attributed to the replacement of Pseudomonas by another pathogen (Proteus morganii or Klebsiella pneumoniae). This study suggests that azlocillin is of value in the treatment of bronchopulmonary infections caused by Ps. aeruginosa.

[Anaphylactic complications due to suxamethonium]. / Accidents anaphylactiques au suxaméthonium.

A study was carried out on 36 patients who had presented with an anaphylactic reaction when they had been received anaesthetic induction agents including suxamethonium. After having been examined, they were assessed with various immunoallergic tests (skin tests, LHL, a search for specific anticholine IgE antibodies). They were compared with a group of 120 control patients with the same age, sex and professional characteristics. This study confirmed the part played by specific IgE antibodies in accidents involving suxamethonium. The specificity of the tests that could be used for the diagnosis was excellent. However, as far as sensitivity of the tests went, skin tests and LHL were more sensitive than the search for specific IgE antibodies. There was no statistical relationship between the limit for skin reactions and the degree of histamine release of the level of anticholine IgE antibody.

[Respiratory allergy and domestic animals. Survey in a sample of the general population]. / Allergie respiratoire et animaux domestiques. Enquêtes réalisées en population générale.

To evaluate the role of exposure to furred pets on respiratory allergic disorders, we interviewed 10,338 adults, selected at random from communities of South-East France. All subjects answered a standardized questionnaire related to asthma and perennial rhinitis and to present or past exposure to furred pets and respiratory symptoms related to this exposure. Besides, a sample of the population had a blood analysis for detection of specific IgE directed against common aero-allergens (Phadiatop). Overall, more than half of the households had a pet, more often in rural than urban communities. Among asthmatics 9.3% acknowledged respiratory symptoms when exposed to pets and 5.9% had parted from their pets because of respiratory symptoms; among patients with chronic rhinitis, those figures were 5.1% and 2.6%, respectively. However, these subjects with respiratory symptoms had pets as often as the whole population. In atopic subjects (positive Phadiatop test), exposed to cats, the prevalence of perennial rhinitis was higher than in atopic subjects not exposed to cats and in non-atopic subjects. Thus furred pets have a deleterious influence on patients with asthma or rhinitis, especially in the atopic subgroup. Pet avoidance is an important factor in the management of these diseases.

[Is there an urban factor in asthma and allergy?]. / Existe-t-il un facteur urbain dans l'asthme et l'allergie?

To evaluate if an "urban factor" could be responsible for an increase of asthma and allergic diseases in developed countries, we compared prevalence rates for these conditions in adults living in urban and rural settings. The urban group consisted of 4,008 adults, randomly selected from the 16 districts of the city of Marseille; the rural group consisted of 1,789 adults, representing 85% of the target population living in a small residential town, Trets. The protocol included, after a mass media information, home-visits by public health physicians. These physicians asked a short standardized questionnaire to all adults 18 to 65 years old. Then, in a subgroup of, hay-fever patients, they performed skin tests to grass pollens. The standardized prevalence rates of asthma and related symptoms, and hay fever, was very similar in both settings. Thus, this study does not support the hypothesis that there is a urban factor in asthma and allergic diseases. In the literature, several studies point out a higher prevalence of these diseases in an urban setting. But these studies have been performed several years ago, when there was a larger difference in air pollutants concentrations between urban and rural settings.

[Therapeutic importance and tolerance of coated 50 mg Vectarion tablets (almitrine bismesylate) at a dosage of 100 mg/day. Study of blood gas, clinical and biological results after a year of long-term treatment]. / Intérêt thérapeutique et acceptabilité du Vectarion 50 mg comprimés enrobés (bismésilate d'almitrine) à la dose de 100 mg/jour. Etude des résultats gazométriques, cliniques et biologiques en traitement prolongé pendant 1 an.

The objectives of this study, in which Almitrine bismesylate was administered for one year in chronic bronchitics with obstructive hypoxia, were to assess its clinical and gasometric efficacy and its clinical, laboratory, spirometric and electrocardiac acceptability. The blood gas results show a significant rise in PaO2 (p less than 0.001) rising by 5.5 mmHg after 6 months (T6) and by 6.0 mmHg after 12 months (T12) in comparison with the value at the study's onset. The PaCO2 fell by 3.3 mmHg at T6 and 2.7 mmHg at T12 (p less than 0.001). The dyspnoea of the patient, scored by the doctor on a scale of severity from 0 to 5 was situated on a mean of 3.3 points at the beginning of the study. It was significantly reduced by 0.8 points at T6 and by 0.9 points at T12 (p less than 0.001). The percentage of patients hospitalised during the course of the study fell significantly in comparison with the previous year, from 68% to 49% (p less than 0.001). The improvement in clinical status and in blood gases bore no relation to changes in respiratory function. The clinical acceptability of the product was good; few side effects were observed and the respiratory, digestive and neurological problems were often pre-existing. They only led to cessation of treatment in three cases. The electrocardiogram was unchanged. The laboratory investigations was unchanged, with the exception of a fall in red blood cells in relation to the correction of the hypoxaemia in polycythaemic patients.