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Biomedical subjects

Alan L James

Publications and source records attributed to Alan L James.

11 recordsLinked to original sources

Abnormalities of the bronchial arteries in asthma.

STUDY OBJECTIVES: The bronchial arteries supply systemic blood to the airways, tracheobronchial lymph nodes, and nerves. Their structure has not been studied in patients with asthma. DESIGN: Case-control study of pathologic changes of bronchial arteries in asthma. PARTICIPANTS AND METHODS: Postmortem lungs were examined from three case groups: (1) fatal asthma (n = 12), death due to asthma; (2) nonfatal asthma (n = 12), asthmatic and death due to nonrespiratory causes; and (3) nonasthmatic control subjects (n = 12), no history of asthma and death due to nonrespiratory causes. In bronchial arteries with outer diameters of 0.1 to 1.0 mm, the areas of lumen, intima, and media were measured and compared between case groups. RESULTS: There were no significant differences in artery size (outer diameter) or in medial area between the three groups. In the two asthma groups, the intimal area was increased (p < 0.05), with a corresponding decrease in luminal area compared with the control group. There was a significant effect of gender, age, and smoking on intimal area. In the asthma cases, the area of bronchial artery intima was related to duration of asthma (p < 0.05), and this increase was associated with smooth muscle proliferation, reduplication, and calcification of the elastica, but not with inflammatory cell infiltration. CONCLUSIONS: While the pathophysiologic significance of these changes is uncertain, the relation to duration of asthma, age, and smoking suggests a secondary response to chronic airway disease.

Adolescent↗

What can Busselton population health surveys tell us about asthma in older people?

WHAT WE NEED TO KNOW: Do the characteristics of asthma differ in people older than 55 years compared with younger people with respect to risk factors (atopy, airway hyper-responsiveness and genetic variation), smoking, lung function and other illness? How do inflammation and remodelling of airways vary with age and with duration and severity of asthma? WHAT WE NEED TO DO: Continue collecting prevalence data for asthma and its risk factors. Assess (i) period and cohort effects on asthma and its risk factors and (ii) interactions between age, smoking, severity and duration of asthma, lung function and airway responsiveness, and other concurrent disease. Measure airway responsiveness and exhaled nitric oxide to detect airway abnormalities in older people and relate this to the diagnoses of asthma and other diseases.

Adult↗

Comparison of sputum induction using inhaled methacholine or hypertonic saline.

OBJECTIVES: Hypertonic saline is recommended for the induction of sputum to assess airway inflammation. Methacholine is most commonly used to assess airway responsiveness. The aim of this study was to compare sputum induction by methacholine and hypertonic saline challenges, and the subsequent inflammatory cell differential counts. METHODOLOGY: Subjects (n = 56) underwent inhaled hypertonic saline (4.5% for < or = 15 min without bronchodilator pretreatment) and methacholine (maximum cumulative dose 4 micromol) challenges 1 week apart, in random order. Sputum was processed, and on cytospins stained with May-Grunwald-Giemsa, a total of 400 inflammatory plus squamous cells were counted to obtain a differential cell count. RESULTS: A satisfactory sputum sample was obtained from 29 subjects following hypertonic saline and also from 10 subjects following methacholine. For these 10 subjects, the mean percent macrophages, neutrophils, eosinophils, and lymphocytes were similar after methacholine (64%, 26%, 7% and 1%) or hypertonic saline (67%, 26%, 6% and 1%). The results were similar for squamous cells (42% and 45%) and when asthmatics and nonasthmatics were compared separately. CONCLUSIONS: Inhaled methacholine has a much lower yield of sputum induction compared with hypertonic saline. However, the differential sputum cell count is similar following both challenge agents.

Adult↗

Correlates of habitual snoring and witnessed apnoeas in Busselton, Western Australia.

OBJECTIVE: The aim of this study was to identify potential body size, behavioural and respiratory risk factors for habitual snoring and witnessed apnoeas in a general population. METHODS: Correlates of these conditions were studied in a sample of 3,577 adults aged 25-74 years who participated in a comprehensive health survey in Busselton, Western Australia, during 1994/95. Logistic regression was used to assess associations after age and gender adjustment and also in multivariate models. RESULTS: The prevalence of both conditions was higher in men and rose with age. After controlling for age, gender and body mass index no additional body size variable remained significantly associated with witnessed apnoeas, whereas both waist-hip ratio and neck-height ratio remained significantly associated with habitual snoring. Among behavioural variables, smoking showed the strongest association, and among respiratory symptoms, asthma for habitual snoring and bronchitis for witnessed apnoeas had significant independent associations. CONCLUSIONS AND IMPLICATIONS: This study has confirmed obesity and smoking as key determinants of habitual snoring and witnessed apnoeas. It has also shown that a number of measures of obesity are independently related to habitual snoring and that asthma and bronchitis may also play a role, independently of obesity.

Adult↗

Decline in lung function in the Busselton Health Study: the effects of asthma and cigarette smoking.

Asthma in adults may be associated with chronic airflow obstruction, possibly resulting from airway disease in early life and/or a greater rate of decline in lung function in adult life compared with those with asthma. Treatment and cigarette smoking may also influence the rate of decline of lung function. The aim of this analysis was to examine the level and rate of decline in lung function in relationship to asthma and cigarette smoking in adults. Subjects (n = 9,317) had participated as adults (> 18 years) in one or more of the cross-sectional Busselton Health Surveys between 1966 and 1981 or in the follow-up study of 1994/1995. The effects of sex, doctor-diagnosed asthma, smoking status, and anthropometric data on the level and rate of decline in FEV1 were examined in a linear mixed effects model. At the age of 19 years, FEV1 was reduced in subjects with asthma but was similar in smokers and nonsmokers. Males, taller subjects, smokers, and subjects with asthma had greater declines in FEV1 with age. Smoking and asthma had additive but not multiplicative effects on decline. Thus, asthma is associated with reduced lung function at the beginning of adult life as well as an increased rate of decline during adult life.

Adult↗

Aggregations of lymphoid cells in the airways of nonsmokers, smokers, and subjects with asthma.

Persistent airway inflammation is present in cases with asthma and in smokers with airflow obstruction. Isolated aggregations of lymphoid cells (IALC) may be sites of localized inflammatory cell activation. Their distribution and characteristics in cartilaginous airways were assessed in postmortem tissue from nonsmokers (n=10), smokers (n=9), and cases of nonfatal (n=10) and fatal asthma (n=10). IALC were present in 70-100% of cases, were more often in proximal than distal airways, and 80% were confined to the outer airway wall. IALC with area greater than 0.1 mm2 were more frequent in both asthma groups (p<0.001). Airways with IALC had increased airway dimensions and greater numbers of eosinophils and lymphomononuclear cells. Within IALC, T and B lymphocytes were segregated and comprised more than 90% of all cells. Proliferating, apoptotic, and antigen-presenting cells (Rel B+ and HLA-DR+) were less than 5%, 30-40%, and less than 1% of all cells, respectively, and were similar in each case group. Vascular structures were increased (p < 0.01) in cases of fatal asthma. These findings show that, even in nonsmoking cases and cases without asthma, IALC are common, show cellular organization, and are associated with airway wall inflammation and remodeling. It remains to be determined if IALC contribute to or result from persistent airway inflammation in asthma.

Adult↗

On the terminology for describing the length-force relationship and its changes in airway smooth muscle.

The observation that the length-force relationship in airway smooth muscle can be shifted along the length axis by accommodating the muscle at different lengths has stimulated great interest. In light of the recent understanding of the dynamic nature of length-force relationship, many of our concepts regarding smooth muscle mechanical properties, including the notion that the muscle possesses a unique optimal length that correlates to maximal force generation, are likely to be incorrect. To facilitate accurate and efficient communication among scientists interested in the function of airway smooth muscle, a revised and collectively accepted nomenclature describing the adaptive and dynamic nature of the length-force relationship will be invaluable. Setting aside the issue of underlying mechanism, the purpose of this article is to define terminology that will aid investigators in describing observed phenomena. In particular, we recommend that the term "optimal length" (or any other term implying a unique length that correlates with maximal force generation) for airway smooth muscle be avoided. Instead, the in situ length or an arbitrary but clearly defined reference length should be used. We propose the usage of "length adaptation" to describe the phenomenon whereby the length-force curve of a muscle shifts along the length axis due to accommodation of the muscle at different lengths. We also discuss frequently used terms that do not have commonly accepted definitions that should be used cautiously.

Animals↗

Airway alveolar attachment points and exposure to cigarette smoke in utero.

The harmful effects of in utero cigarette smoke exposure include increased asthma symptoms and reduced lung function during the neonatal period, increased airway responsiveness to inhaled stimuli, and an increased risk of sudden infant death syndrome. Altered lung function may result from altered airway/lung structure. Airway dimensions, alveolar attachment points, and parenchymal elastin content were measured in 32 infants who died from sudden infant death syndrome and were grouped according to their perinatal cigarette smoke exposure. Compared with those without any exposure to cigarette smoke, the distance between alveolar attachments on airways was greater (p < 0.001) in infants exposed to cigarette smoke only in utero or both in utero and during the postnatal period but not different in those with only postnatal exposure. The percentage of elastin within the alveolar walls was similar in all the exposure groups. These findings suggest that in utero cigarette smoke exposure may result in abnormal airway function due to a reduction of the forces opposing airway narrowing.

Bronchi↗

The relationship of reticular basement membrane thickness to airway wall remodeling in asthma.

Assessment of airway wall remodeling in asthma is difficult in vivo. The thickness of deposited extracellular matrix proteins below the epithelium, the reticular basement membrane, can be assessed by bronchial biopsy of proximal airways. The aim of this study was to determine the relationship between the thickness of the reticular basement membrane in a sample equivalent to a central airway biopsy and the dimensions of the airway wall measured on transverse sections of both central and peripheral airways. Large and small cartilaginous and membranous airways from persons who had died from asthma (fatal asthma, n = 5) or from nonrespiratory causes with asthma (nonfatal asthma, n = 5) or without asthma (control subjects, n = 5) were studied. Reticular basement membrane thickness correlated with the percentage of smooth muscle, submucosal mucous gland, and inner wall area (p < 0.05) in large cartilaginous airways, and with inner wall area and area of smooth muscle (p < 0.01) in small cartilaginous airways, but was not related to airway wall dimensions in membranous airways. These findings show that reticular basement membrane thickness of central airways, which may be assessed by endobronchial biopsy, is correlated with airway remodeling in cartilaginous airways but not with airway wall dimensions of membranous airways.

Adult↗

Peripheral airways in asthma.

The peripheral, or small, airways are usually defined as conducting airways that are less than 2 mm in internal diameter and extend from the noncartilaginous bronchioles to the alveolar ducts. Noninvasively measuring the function of the small airways in isolation is difficult since they make up only about 10% of total airway resistance. Quantitative pathologic studies have shown that both the small and large airways are involved in inflammation and remodeling in asthma. Recent studies also have shown that inflammation involves the alveoli surrounding small airways in asthma and that the distribution of different inflammatory cells across the airway wall varies in both large and small airways. Inhaled treatment that targets the small airways may be more effective than treatment that is deposited more proximally and suggests that treatments in the future need to address the variable distribution of pathology in the bronchial tree in asthma.

Airway Resistance↗

Respiratory morbidity and lung function in two Aboriginal communities in Western Australia.

OBJECTIVE: To examine differences in the rates of respiratory symptoms, asthma and levels of lung function in two remote Aboriginal communities. METHODOLOGY: Respiratory symptoms, smoking history, skin prick test responses to common allergens, serum IgE, lung function, airway responsiveness to methacholine and white blood cell counts were compared in two Aboriginal communities, one from the central desert (n = 84) and another from the tropical north (n = 209) of Western Australia. RESULTS: Compared with the tropical community, chest tightness and dyspnoea were more frequent and forced expiratory volume in 1 s and forced vital capacity were lower in the desert community, despite similar levels of wheeze, doctor-diagnosed asthma and skin prick test responses and lower levels of airway responsiveness and smoking. The total white cell and neutrophil counts were greater in the desert community. Serum IgE was very high and similar in both communities. CONCLUSIONS: Our findings show a low prevalence of asthma in children, a high prevalence of respiratory symptoms and low levels of lung function in remote Aboriginal communities. The greater prevalence of respiratory morbidity in the desert community was not explained by diagnosed asthma, airway hyperresponsiveness or cigarette smoking. The role of infection requires further investigation. The results suggest that the lower lung function observed in Aboriginal communities (compared with non-Aboriginal communities) results at least partly from environmental factors.

Adolescent↗