The role of smooth muscle in determining human non-specific bronchial responsiveness

This project tested the hypothesis that variation in non specific bronchial responsiveness between individuals could be explained by differences in the sensitivity of the smooth muscle present in the airway. Non-specific bronchial responsiveness (NSBR) is closely associated with asthma and chronic airflow obstruction. The approach used was to measure the NSBR of patients due to undergo thoracic surgery, and compare this with the in vitro sensitivity of bronchial strips obtained from thoracotomy specimens. In vivo measurements: The first part of the project was devoted to developing methods and protocols to measure changes in airway calibre so that responsiveness could be measured. FEV1 is a reliable measure of airway calibre, but reflects overall airway function. As the in vitro measurements were made on larger airways, changes in specific airways conductance (sGAW) were used because they reflect changes in the larger airways. The measurement of sGaw by hand was time consuming and the measurement had large co-efficient of variation. To overcome these problems an automated system for the measurement of sGaw was developed. The second study looked at LTD4 induced bronchconstriction in asthmatic patients, and the effect of verapamil and sodium cromoglycate on this. The asthmatic subjects were more responsive to LTD4 by a factor of 10, but in contrast with the normal subjects verapamil did not inhibit LTD4 induced bronchoconstriction. Possible reasons for this difference are discussed. LTD4 was used as the agonist in the in vivo responsiveness and in vitro sensitivity protocol. There was no relationship between in vivo responsiveness and in vitro sensitivity. In this study the amount of smooth muscle present in the bronchial strips was measured. The quantity of smooth muscle present correlated significantly with the maximum tension produced in vitro but neither muscle quantity nor tension generated per unit mass of muscle was related to in vivo responsiveness. This result suggests that smooth muscle hypertrophy may contribute to NSBR. Using 3 bronchconstrictor agents no relation was found between in vivo NSBR and in vitro smooth muscle. Two asthmatic patients were responsive by in vivo criteria, but smooth muscle obtained from them did not have increased sensitivity. The final chapter of the thesis examines whether passive sensitisation of muscle, to render it atopic as in allergic asthma, alters in vitro sensitivity to histamine. Neither sensitisation per se, nor sensitisation followed by specific allergen challenge altered in vitro sensitivity of human airway smooth muscle. In conclusion, airway smooth muscle sensitivity is not the sole/ sole determinant of NSBR. Smooth muscle hypertrophy did not relate to in vivo responsiveness, although this result was obtained in patients with C. A. O. who may have different mechanisms for NSBR. Increased NSBR is due to a complex interaction between smooth muscle, neural and humoral factors

Lung function and bronchial responsiveness in preschool children

It is hypothesized that childhood asthma, especially when not well controlled, may constitute a risk factor for the development of COLD in adulthood (Cropp, 1985), It is unknown whether lung injury during early life is a risk factor for the development of COLD in adulthood, Asthma often starts before schoolage (Cropp, 1985), Except for the disturbing symptoms, a reason for paying attention to asthma in preschool children is the hypothesis that adequate intervention may reduce the risk of COLD in adult life (Kerrebijn, 1982). To detect lung function abnormalities at as young as possible ages suitable methods should be available. Most lung function methods can only be performed in children over 6 years of age. Lung function was measured with the forced pseudo-random noise oscillation technique (FOT) (Uindser et al., 1976a) because only passive cooperation is needed. Resistance (R,) and reactance (X,) of the respiratory system are simultaneously measured over a frequency spectrum of 2 to 26 Hz. R, is mainly determined by the patency of the upper and large airways. X, is influenced by mass-inertial and elastic properties of the respiratory system. The applicability ofFOT in preschool children was investigated. The method is now suitable for use in clinical practice to measure lung function and BR in children from about 2lfz years of age. We measured airway patency, bronchial smooth muscle tone and BR in preschool asthmatic children. Secondly, we investigated whether lung injury during early influences the development of lung function and bronchial responsiveness in children who do not have a genetic predisposition of asthma. This was investigated in children who had infant bronchiolitis, in subjects who survived infant bronchopulmonary dysplasia after neonatal respiratory distress syndrome and in individuals who experienced a near-drowning accident. The results are compared to data found in healthy controls

Korttidsstudie av sammenhengen mellom luftforurensninger og helsevirkninger i Grenland - Hovedrapport.

Rapporten oppsummerer forskjellige deler av kohortundersøkelsen om korttidshelseeffektene av luftforurensninger i et industriområde. For hvert individ ble det på timebasis beregnet eksponering for SO2, NO2, O3, sulfater, nitrater, finfraksjonert støv, basert på informasjonen fra de enkeltes dagbøker kombinert med geografiske modeller av luftforurensninger, kontinuerlige målinger på 5 stasjoner og målinger utført innendørs/utendørs. Selvrapporterte subjektive og objektive helsedata ble samlet fra 400 deltakere med og uten lungesykdom. Forandringer i lungefunksjonen (PEF) knyttet til forurensning ble ikke påvist. Sammenhenger ble funnet mellom subjektive helseplager og nitrat, O3, og til dels sulfat, NO2 og SO2

The INDEX Project - Critical Appraisal of the Setting and Implementation of Indoor Exposure Limits in the EU

The INDEX project (Critical Appraisal of the Setting and Implementation of Indoor Exposure Limits in the EU), coordinated by the EU/JRC and funded by DG SANCO, has been finished in December 2004. The project was carried out in collaboration with a Steering Committee of leading European experts in the area of indoor air pollution. Scope of INDEX was to identify priorities and to assess the needs for a Community strategy and action plan in the area of indoor air pollution. The key issues that have been addressed within the project are: - the setting up of a list of compounds to be measured and regulated in indoor environments with priority, on the basis of health impact criteria - to provide suggestions and recommendations on potential exposure limits for these compounds and - to provide information on links with existing knowledge, ongoing studies, legislation etc. at world scale. Suggestions and recommendations on potential exposure limits or other exposure control actions were defined for five prioritised compounds; formaldehyde, nitrogen dioxide, carbon monoxide, benzene, and naphthalene.JRC.I.5-Physical and chemical exposure