Diagnostic morphometry in emphysema and chronic bronchitis

A morphometric technique of point counting was developed for macroscopic use in emphysematous lungs and microscopic use in bronchi to obtain actual areas and volumes, as opposed to ratios or percentages, of emphysema and submucosal glands. The results in emphysematous lungs showed that the volume of emphysema seen in one slice of one lung cannot be used to predict the volume in other slices, nor the volume of emphysema in one lung to predict the volume of emphysema in the other. The results in the airways showed that, if the volume of bronchial glands in each generation along an airway is expressed per unit of luminal surface area, a distinctive profile of gland distribution along the airway is obtained, as well as the mean volume per gland. These results are discussed in relation to the application of morphometry in individual cases for diagnostic purposes, revealing a need for a central repository of validated methods, so that each method is not repeatedly revalidated, and normal baseline data for the diagnostic morphometrist to use in deciding whether the findings in his or her individual patients are of diagnostic significance.     

Pulmonary endocrine cells in chronic bronchitis and emphysema

A r?le for pulmonary endocrine cells has been suggested in the response of the lungs to hypoxia, the control of the pulmonary vasculature and inflammatory pulmonary disease. Since hypoxia, inflammation and vascular remodelling are all central to the pathology of chronic bronchitis and emphysema, we have studied these cells in the lungs of subjects with this condition. In comparison with lungs of matched controls, there was a modest uniform increase in endocrine cells containing gastrin-releasing peptide, possibly associated with vascular remodelling, and a marked increase in cells containing calcitonin, which was particularly seen in consolidated lobes and possibly related to inflammation.     

Carbon monoxide and exercise tolerance in chronic bronchitis and emphysema.

The effects of carbon monoxide on exercise tolerance as assessed by the distance walked in 12 minutes were studied in 15 patients with severe chronic bronchitis and emphysema (mean forced expiratory volume in one second 0.56 1, mean forced vital capacity 1.54 1). Each subject walked breathing air and oxygen before and after exposure to sufficient carbon monoxide to raise their venous carboxyhaemoglobin concentration by 9%. There was a significant reduction in the walking distance when the patients breathed air after exposure to carbon monoxide (p less than 0.01), and the significant increase in walking distance seen after exercise when breathing oxygen at 2 1/minute via nasal cannulae was abolished if carbon monoxide has previously been administered. Thus concentrations of carboxyhaemoglobin frequently found in bronchitic patients who smoke may reduce their tolerance of everyday exercise, possibly by interfering with the transport of oxygen to exercising muscles.     

The use of hypoxic stimulation in chronic and relapsing bronchitis in young children ]

214 children of different age with various forms of bronchitis were subject to immunological and biochemical examination. Against a background of hypoxic state of patients the values of quantitative indices of cellular immunity (E-RFC, blast-transformation reaction with phytohemagglutination) were revealed to decrease and dysimmunoglobulinemia-to form. It is shown that in the period of exacerbation of clinical symptoms of bronchitis the concentration of malonic dialdehyde and resistance of erythrocyte membranes to peroxide hemolysis significantly increase. Analysis of peroxidation level against a background of improvement of clinical indices after the performed treatment indicates that there is no tendency to normalization of metabolic disorders. The above results show that it is necessary to carry out normobaric hypoxic stimulation aimed at treating and preventing bronchitis in children of early age.     

Mechanism of exercise-induced hypoxemia in horses

Arterial hypoxemia has been reported in horses during heavy exercise, but its mechanism has not been determined. With the use of the multiple inert gas elimination technique, we studied five horses, each on two separate occasions, to determine the physiological basis of the hypoxemia that developed during horizontal treadmill exercise at speeds of 4, 10, 12, and 13-14 m/s. Mean, blood temperature-corrected, arterial PO2 fell from 89.4 Torr at rest to 80.7 and 72.1 Torr at 12 and 13-14 m/s, respectively, whereas corresponding PaCO2 values were 40.3, 40.3, and 39.2 Torr. Alveolar-arterial PO2 differences (AaDO2) thus increased from 11.4 Torr at rest to 24.9 and 30.7 Torr at 12 and 13-14 m/s. In 8 of the 10 studies there was no change in ventilation-perfusion (VA/Q) relationships with exercise (despite bronchoscopic evidence of airway bleeding in 3) and total shunt was always less than 1% of the cardiac output. Below 10 m/s, the AaDO2 was due only to VA/Q mismatch, but at higher speeds, diffusion limitation of O2 uptake was increasingly evident, accounting for 76% of the AaDO2 at 13-14 m/s. Most of the exercise-induced hypoxemia is thus the result of diffusion limitation with a smaller contribution from VA/Q inequality and essentially none from shunting.     

Systematic review with meta-analysis of the epidemiological evidence relating smoking to COPD, chronic bronchitis and emphysema

Background

Smoking is a known cause of the outcomes COPD, chronic bronchitis (CB) and emphysema, but no previous systematic review exists. We summarize evidence for various smoking indices.

Methods

Based on MEDLINE searches and other sources we obtained papers published to 2006 describing epidemiological studies relating incidence or prevalence of these outcomes to smoking. Studies in children or adolescents, or in populations at high respiratory disease risk or with co-existing diseases were excluded. Study-specific data were extracted on design, exposures and outcomes considered, and confounder adjustment. For each outcome RRs/ORs and 95% CIs were extracted for ever, current and ex smoking and various dose response indices, and meta-analyses and meta-regressions conducted to determine how relationships were modified by various study and RR characteristics.

Results

Of 218 studies identified, 133 provide data for COPD, 101 for CB and 28 for emphysema. RR estimates are markedly heterogeneous. Based on random-effects meta-analyses of most-adjusted RR/ORs, estimates are elevated for ever smoking (COPD 2.89, CI 2.63-3.17, n = 129 RRs; CB 2.69, 2.50-2.90, n = 114; emphysema 4.51, 3.38-6.02, n = 28), current smoking (COPD 3.51, 3.08-3.99; CB 3.41, 3.13-3.72; emphysema 4.87, 2.83-8.41) and ex smoking (COPD 2.35, 2.11-2.63; CB 1.63, 1.50-1.78; emphysema 3.52, 2.51-4.94). For COPD, RRs are higher for males, for studies conducted in North America, for cigarette smoking rather than any product smoking, and where the unexposed base is never smoking any product, and are markedly lower when asthma is included in the COPD definition. Variations by sex, continent, smoking product and unexposed group are in the same direction for CB, but less clearly demonstrated. For all outcomes RRs are higher when based on mortality, and for COPD are markedly lower when based on lung function. For all outcomes, risk increases with amount smoked and pack-years. Limited data show risk decreases with increasing starting age for COPD and CB and with increasing quitting duration for COPD. No clear relationship is seen with duration of smoking.

Conclusions

The results confirm and quantify the causal relationships with smoking.