Innate immunity in cystic fibrosis lung disease.

Chronic lung disease determines the morbidity and mortality of cystic fibrosis (CF) patients. The pulmonary immune response in CF is characterized by an early and non-resolving activation of the innate immune system, which is dysregulated at several levels. Here we provide a comprehensive overview of innate immunity in CF lung disease, involving (i) epithelial dysfunction, (ii) pathogen sensing, (iii) leukocyte recruitment, (iv) phagocyte impairment, (v) mechanisms linking innate and adaptive immunity and (iv) the potential clinical relevance. Dissecting the complex network of innate immune regulation and associated pro-inflammatory cascades in CF lung disease may pave the way for novel immune-targeted therapies in CF and other chronic infective lung diseases.

Multiple primary bronchogenic carcinomas: treatment and follow-up.

A second primary bronchogenic carcinoma subsequently developed 8 to 156 months later in 19 patients who underwent curative resection of primary bronchogenic carcinomas. The second primary tumor was treated by surgical resection in 9 patients, 3 patients' tumors were considered unresectable, and the remaining 7 patients, despite having potentially resectable tumors, did not undergo resection because of insufficient pulmonary reserve or unwillingness to undergo resection. Actuarial life-table analysis of survival for the 9 patients who underwent resection showed a median survival time of 110.3 months compared with 19 months for the group with unresected but resectable tumors and 10.5 months for the group with unresectable tumors. There was no operative mortality in the group with resected tumors. We conclude that in patients in whom a second primary carcinoma of the lung develops, surgical resection prolongs survival and can be performed with a low operative mortality.

Respiratory muscle weakness and dyspnea in thyrotoxic patients.

Dyspnea on exertion is a frequently reported symptom of thyrotoxicosis. In the majority of cases, there is no obvious cause of dyspnea, but as skeletal myopathy is also common in thyrotoxic patients, it has been postulated that increased dyspnea could be secondary to respiratory muscle weakness. We sought to determine whether thyrotoxic patients were in fact more dyspneic on exertion than age- and sex-matched controls, and if so, whether the increased dyspnea was secondary to respiratory muscle weakness. The study group consisted of 12 thyrotoxic patients and 12 control subjects matched for age and gender. We measured lung volumes, compliance, elastic recoil, respiratory muscle strength, maximal exercise performance, and the intensity of breathlessness (modified Borg scale) at various levels of exercise in all subjects. The respiratory muscles were weaker in patients than controls. This weakness improved in treated patients (p less than 0.05) with concomitant increases in VC, IC, and TLC (all p less than 0.05). Despite this, we found no differences in breathlessness intensity scores between patients and controls or in patients before and after successful antithyroid therapy.

Comparison of two-minute incremental threshold loading and maximal loading as measures of respiratory muscle endurance.

We performed a two-minute incremental threshold loading test (incremental test) in ten normal subjects on three occasions, and having ascertained the maximum load (max load) against which they could inspire for two minutes, measured how long this load could be tolerated by these same subjects on three further occasions (tlim test). We compared the reproducibility of the two tests. There were no significant differences found in the mean max loads in the three incremental tests, or in the endurance times in the three tlim tests. However, the intraindividual coefficients of variation of max load in the incremental test (0 to 14 percent) were much smaller than the intraindividual coefficients of variation of endurance time in the tlim test (20 to 65 percent). We found that the large variability in endurance time in our tlim tests was most likely accounted for by variability in breathing pattern, inspiratory flow rate and breath-by-breath mouth pressure generation. Differences in these parameters did not, however, explain why in the tlim test a given subject could tolerate for 19 minutes a load only 100 g less than that which he was unable to tolerate for two minutes in the incremental test. These findings emphasize the differences between these two tests of respiratory muscle endurance. Since there was less intraindividual variability in the two-minute incremental threshold loading test, we suggest that this test may be more useful than the tlim test.

Prediction of maximal oxygen uptake and power during cycle ergometry in subjects older than 55 years of age.

One hundred twenty-eight healthy volunteers (81 women, 47 men) older than 55 yr of age were studied with an incremental progressive cycle ergometer test to a symptom-limited, maximal tolerable work load. Mean (+/- SD) age was 66 +/- 6 yr in women and 66 +/- 5 years in men. Subjects with a history of ischemic heart disease, diabetes, pulmonary disease, or neuromuscular disease were excluded. Smokers were included, but all subjects had normal FEV1 and FVC. The objective of the study was to compare measured values of VO2max and Wmax in this older population with previously published predicted values based on subjects of all ages. We found that Wmax observed exceeded Wmax predicted by 9.5 +/- 22% (mean +/- SD) and that VO2max observed exceeded VO2max predicted by 17.5 +/- 22%. Because of this systematic underestimate of VO2max and Wmax by the previous prediction equations, we constructed new prediction equations for use in subjects older than 55 yr of age using height, weight, age, and sex as variables. We conclude that these new prediction equations more accurately predict Wmax and VO2max in subjects older than 55 yr of age because they are based solely on subjects in this age group.

Cardiac output at rest and in exercise in elderly subjects.

We measured cardiac output (Q), at rest and during graded exercise, in 68 women and 41 men over the age of 55 yr, using a CO2 rebreathing method. Mean (+/- SD) age was 66 +/- 5 yr in women and 66 +/- 6 yr in men. Only subjects with no history or physical examination findings of pulmonary, cardiac, neuromuscular, or endocrine disease and normal electrocardiography and spirometry were studied. We found a linear relationship between Q and oxygen uptake (VO2) in males and females. The regression equation expressing this relationship in males was Q = 2.9 + 5 VO2 1.min-1 (SEE 2.8) and, in females, Q = 2.9 + 4.6 VO2 1.min-1 (SEE 2.8). This is similar to the relationship previously estimated for elderly males using the direct Fick method and concurs with other reports in the literature which show that, while the Q-VO2 relationship in the elderly has a slope similar to that in younger groups, the Q-VO2 intercept is lower. This means that the absolute level of cardiac output for a given level of work is lower in the elderly than in younger populations. This may reflect an age-related decrease in active metabolic tissue in the elderly and/or altered metabolic regulation with increased oxygen extraction from blood.

Multicentricity of adenocarcinoma of the lung.

In a consecutive series of 62 lung resections for bronchogenic adenocarcinoma, 12 patients (19 percent) were found to have two or more adenocarcinomas on careful pathologic examination. These tumors all met the criteria for separate primary malignancy. In only two of the patients were the additional lesions suspected preoperatively. This incidence of multiple primary lung adenocarcinomas in apparently operable patients is several fold higher than would be anticipated from the literature. The phenomenon has important implications for preoperative radiologic evaluation, postoperative pathologic examination, assignment of TNM stage, and clinical follow-up of patients undergoing successful resection.

Maximal static respiratory pressures in the normal elderly.

To determine if a relationship exists between maximal static respiratory pressures measured at the mouth and age greater than 55 yr, and if so, whether regression equations can be derived that accurately reflect this, we measured maximal inspiratory (Plmax) and expiratory (PEmax) pressures in 64 normal women and 40 normal men older than 55 yr of age. We found no relationship between PImax and PEmax and age greater than 55 yr (all r squared values less than 0.14). We tested the reproducibility of our measurements of PImax and PEmax in 13 and 12 subjects, respectively, on three separate occasions. Repeated measures analysis showed no significant differences in these measurements. Using the measurements obtained in this large study, we calculated 95% confidence limits for PImax and PEmax values in men and women older than 55 yr of age. The 95% confidence limits for PImax in men were 55 to 161 cm H2O, and 26 to 124 cm H2O in women. The 95% confidence limits for PEmax in men were 90 to 256 cm H2O, and 46 to 184 cm H2O in women. We conclude that given the large interindividual variation, a cross-sectional study such as this or other previous studies may not be able to reveal age-dependent changes unless very large numbers are used, and even then potential for bias exists. However, with the small intraindividual coefficients of variation in repeated measurements of PImax and PEmax, a longitudinal study may provide more pertinent information.

Surgical management of spontaneous pneumothorax in patients with acquired immunodeficiency syndrome.

Spontaneous pneumothorax has been reported with increasing frequency in patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia. In the past year, we treated 4 patients with spontaneous pneumothorax. All of them were treated with closed tube thoracostomy, and 1 patient with bilateral apical cysts eventually required bilateral thoracotomies and pleurectomies. Only 1 patient had an uncomplicated hospital course. The remaining patients had prolonged air leaks, and 2 had synchronous pneumothoraces. Pneumothorax appears to be associated with P. carinii pneumonia. We recommend closed tube thoracostomy as the initial treatment in symptomatic patients. Pleurectomy for air leaks persisting longer than seven days can be safely performed in patients fit for thoractomy.