Respiration physiology最新文献

For most smokers, tobacco dependence begins in childhood or adolescence. This review summarizes the state of social science with respect to the prevention of tobacco use. Social ecology is introduced as a theoretical framework useful for organizing prevention approaches. In recent years, the field has shifted from approaches directed at individuals, towards appreciation of additional, more comprehensive social and environmental influences on initation. These range from intra-individual factors (including physiological responses to nicotine and the psychology of use) to individual, interpersonal, organizational, community, and population factors affecting access and demand. This review highlights prevention approaches that address social and societal influences, from school programs that attempt to change susceptibility of individual youth to tobacco, to community projects, media campaigns, restrictive policies, and tobacco pricing. The most promising approaches are those designed with input based on extensive formative research including studies with youth, directed at multiple levels of the social ecology, and sustained over time with significant resources and ongoing, multi-sector inputs.

Acute lung inflammation is an important component of a number of pulmonary diseases, including acute respiratory distress syndrome (ARDS). Much has been learned about the manner in which various insults to lung, such as infection or trauma, bring about recruitment of neutrophils into alveoli and small airways, resulting in parenchymal damage and organ dysfunction. In this brief review, we discuss the endogenous mechanisms in which the lung regulates the acute inflammatory response in rats to intrapulmonary deposition of IgG immune complexes. Emphasis is given to the participation of the transcription factor, NF-κB, in the development of lung injury and the endogenous mediators which attempt to control the extent of lung inflammation by modulating the activation of NF-κB.

Prospective longitudinal studies measuring aerosol behavior in the respiratory tract as humans age have not been performed. The present paper reviews observations related to aging of the respiratory tract and other effects more likely due primarily to disease and iatrogenic causes. Upper airway deposition was found to approximate 50% in children during inhalation of drugs thought to be designed primarily for deposition in the lower respiratory tract. In older subjects, aging per se did not have a major impact on the deposition of aerosols. Disease processes that develop with age were shown to be the primary cause of deposition abnormalities. Flow-limitation in central airways was proposed as a major factor responsible for central airway deposition as well as abnormal clearance in common obstructive lung diseases. The oral cavity, a source of pathogenic organisms causing pneumonia, was also studied in the elderly. Salivary clearance, often abnormal in the aged, was related to colonization with pathogenic bacteria. Salivary clearance was not obviously reduced by aging per se but by iatrogenic sources such as drug therapy for other diseases.

Respiratory tract infections, particularly pneumonia, are a leading cause of death in persons 65 years or older in both developed and developing countries. Because many attributes of immunity wane with advancing age, the elderly may be more susceptible to respiratory infections, even if they appear to be in good health. A decline in the ability of lymphoid tissues to mount an antigen-specific response (adaptive immunity) to specific microorganisms such as influenza virus or Streptococcus pneumoniae is thought to be an important factor in increasing susceptibility to respiratory tract infection with advancing age. However, abnormalities in innate immunity may also contribute to increased susceptibility to respiratory infections and have been poorly characterized in the elderly. Although changes in immune parameters such as T cell subsets and immunoglobulin concentrations have been observed in respiratory secretions from older healthy individuals compared to younger subjects, the significance of these changes for protective immunity in the lung is unknown. The incidence of pneumonia may be lessened by measures such as optimizing treatment of comorbid conditions, optimizing nutrition, and addressing swallowing disorders. The use of vaccines directed against the influenza virus and S. pneumoniae appears to have made an impact on the degree of morbidity and mortality, and perhaps, the incidence, of community-acquired pneumonia. However, better stimulation of specific immune responses with improved vaccines and more widespread use of these vaccines for protection of elderly individuals are needed.

Despite the tremendous inter-individual variability in the response to inhaled toxins, we simply do not understand why certain people develop disease when challenged with environmental agents and others remain healthy. To address this concern, we investigated whether the toll-4 (TLR4) gene, that has been shown to affect lipopolysaccharide (LPS) responsiveness in mice, underlies the variability in airway responsiveness to inhaled LPS in humans. Here we show that common, co-segregating missense mutations (Asp299Gly and Thr399Ile) in the extracellular domain of the TLR4 receptor are associated with a significantly blunted response to inhaled LPS in 83 humans. Transfection of THP-1 cells demonstrates that the Asp299Gly mutation (but not the Thr399Ile mutation) interrupts TLR4-mediated LPS signaling. Moreover, the wild type allele of TLR4 rescues the LPS hyporesponsive phenotype in either primary airway epithelial cells or alveolar macrophages obtained from individuals with the TLR4 mutations. Our findings provide the first genetic evidence that common mutations in TLR4 are associated with differences in LPS responsiveness in humans, and demonstrate that gene sequence changes can alter the ability of the host to respond to environmental stress.

There is renewed interest in inhalation toxicology regarding ‘susceptibility’ as associated with host variables, including genetics, age, diet, and disease. This interest derives from epidemiology that shows air pollution-related human mortality/morbidity, especially among individuals with cardiopulmonary disease. Several animal models with experimental or genetically-based cardiopulmonary diseases are now being incorporated into inhalation toxicology studies to investigate mechanisms that underlie host susceptibility. However, current models have strengths and limitations as to how they mimic the essential features of human diseases. To date, animal models of pulmonary hypertension, bronchitis, asthma, and cardiovascular disease, but not emphysema, appear to exhibit greater susceptibility to air pollution particulate matter. As in humans, host susceptibility appears to involve multiple genetic and environmental factors, and is poorly understood, but the database of information is growing rapidly. As existing models gain wider use, our understanding of the models will improve and encourage refinements/development of models that integrate both genetic and environmental factors to better mimic the human condition.

Worksite tobacco control initiatives face a crucial challenge: the growing occupational disparity in smoking prevalence. Blue-collar workers are more likely to be smokers than workers are in white-collar jobs. Blue-collar workers also experience a high prevalence of hazardous exposures on the job. Given these multiple risks, it is imperative that successful comprehensive programs be developed to promote and protect the health of blue-collar workers. Although evidence is still accruing about the efficacy of workplace interventions integrating tobacco control and occupational health, it is possible to identify promising intervention strategies by drawing on the preliminary evidence on effective worksite interventions. The effectiveness of worksite tobacco control interventions will be enhanced when coordinated interventions aim to promote cessation among individual smokers, build social support for quitting and social norms that support non-smoking, engage management in assuring a healthy work environment, involve workers’ families in non-smoking initiatives, and provide links to community and public policy initiatives that support tobacco control as well as a broader effort promoting worker health.

Mechanoreflexes that activate genioglossus electromyogram (EMGgg) in response to negative upper airway pressure (UAP) may help defend airway patency in obstructive sleep apnea. Hypercapnia may affect mechanoreflexes by increasing EMGgg response to actively reduce genioglossus length (Lgg, measured by sonomicrometry). We hypothesized that during normocapnia, Lgg would be reduced at positive, and increased at negative UAP but hypercapnia would increase EMGgg responses to negative pressures and cause Lgg reductions. At 0, 3.5 and 7% inhaled CO₂ (balance O₂), Lgg and EMGgg were measured during static negative and positive UAP applied to the isolated upper airway in four unanesthetized goats. At 3.5 and 7% CO₂ EMGgg was significantly increased and Lgg decreased with negative pressure while EMGgg was also greater at 7 than 0% CO₂ (P<0.05). Non-significant pressure related Lgg changes were observed during normocapnia. These results suggest that hypercapnia may stimulate greater mechanoreflex EMGgg activation and consequent Lgg reduction in response to negative UAP application.

We evaluated the effects of a 5 week (25 sessions); (30–35 min/day, 5 days/week), respiratory muscle training (RMT) program in nine competitive male cyclists. The experimental design included inspiratory resistance strength training (3–5 min/session) and hyperpnea endurance training (30 min/session), a placebo group which used a sham hypoxic trainer (n=8), and three exercise performance tests, including a highly reproducible 8 km time trial test. RMT intensity, measured once a week in terms of accumulated inspiratory pressure and the level of sustainable hyperpnea increased significantly after 5 weeks (+64% and +19%, respectively). The RMT group showed a significant 8% increase in maximal inspiratory pressure (P<0.05) while the placebo group showed only a 3.7% increase (P>0.10). RMT and placebo groups both showed significant increases in the fixed work-rate endurance test performance time (+26% and +16%, respectively) and in the peak work-rate achieved during the incremental maximal oxygen consumption () test (+9 and +6%). The 8 km time trial performance increased 1.8±1.2% (or 15±10 sec; P<0.01) in the RMT group with 8 of 9 subjects increasing; the placebo group showed a variable non-significant change in 5 of 8 subjects (−0.3±2.7%, P=0.07). The changes observed in these three performance tests were not, however, significantly different between the RMT and placebo groups. Heart rate, ventilation, or venous blood lactate, at equal work-rates during the incremental exercise test or at equal times during the fixed work-rate endurance test were not changed significantly across these exercise trials in either group. We propose that the effect of RMT on exercise performance in highly trained cyclists does not exceed that in a placebo group. Significant placebo and test familiarization effects must be accounted for in experimental designs utilizing performance tests which are critically dependent on volitional effort.