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(1/4931) A new model rat with acute bronchiolitis and its application to research on the toxicology of inhaled particulate matter.

The aim of the present study was to establish a useful animal model that simulates humans sensitive to inhaled particulate matter (PM). We have developed a new rat model of acute bronchiolitis (Br) by exposing animals to NiCl2 (Ni) aerosols for five days. Three days following the Ni exposure, the animals developed signs of tachypnea, mucous hypersecretion, and bronchiolar inflammation which seemed to progress quickly during the fourth to fifth day. They recovered from lesions after four weeks in clean air. To assess the sensitivity of the Br rats to inhaled particles, two kinds of PM of respirable size were tested with doses similar to or a little higher to the recommended threshold limit values (TLVs) for the working environment in Japan. Titanium dioxide (TiO2 = Ti) was chosen as an inert and insoluble particles and vanadium pentoxide (V2O5 = V), as a representative soluble and toxic airborne material. The Br rats exposed to either Ti or V were compared the pathological changes in the lungs and the clearance of particles to those in normal control or Br rats kept in clean air. The following significant differences were observed in Br rats: 1. delayed recovery from pre-existing lesions or exacerbated inflammation, 2. reductions in deposition and clearance rate of inhaled particles with the progress of lesions. The present results suggest that Br rats are more susceptible to inhaled particles than control rats. Therefore, concentrations of particulate matter lower than the TLVs for Japan, which have no harmful effects on normal lungs, may not always be safe in the case of pre-existing lung inflammation.  (+info)

(2/4931) Cytokines and inflammatory mediators do not indicate acute infection in cystic fibrosis.

Various treatment regimens and difficulties with research design are encountered with cystic fibrosis (CF) because no standard diagnostic criteria exist for defining acute respiratory exacerbations. This study evaluated the role of serial monitoring of concentrations of selected cytokines and inflammatory mediators in serum and sputum as predictors of respiratory exacerbation, as useful outcome measures for CF, and to guide therapy. Interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha), neutrophil elastase-alpha-1-protease inhibitor complex (NE complex), protein, and alpha-1-protease inhibitor (alpha-1-PI) were measured in serum and sputum collected from CF patients during respiratory exacerbations and periods of well-being. Levels of NE complex, protein, and alpha-1-PI in sputum rose during respiratory exacerbations and fell after institution of antibiotic therapy (P = 0.078, 0.001, and 0.002, respectively). Mean (+/- standard error of the mean) levels of IL-8 and TNF-alpha were extremely high in sputum (13,780 +/- 916 and 249.4 +/- 23.5 ng/liter, respectively) but did not change significantly with clinical deterioration of the patient (P > 0.23). IL-8 and TNF-alpha were generally undetectable in serum, and therefore these measures were unhelpful. Drop in forced expiratory volume in 1 s was the only clinical or laboratory parameter that was close to being a determinant of respiratory exacerbation (P = 0.055). This study provides evidence of intense immunological activity occurring continually within the lungs of adult CF patients. Measurement of cytokines and inflammatory mediators in CF sputum is not helpful for identifying acute respiratory exacerbations.  (+info)

(3/4931) Effects of acute prolonged exposure to high-altitude hypoxia on exercise-induced breathlessness.

The direct effects of hypoxia on exercise-induced breathlessness are unclear. Increased breathlessness on exercise is known to occur at high altitude, but it is not known whether this is related to the hypoxia per se, or to other ventilatory parameters. To examine the role of high-altitude hypoxia in exercise-induced breathlessness, studies were performed in 10 healthy, normal subjects at sea level and after acute exposure to an altitude of 4450 m. Although the perception of hand weights did not alter between sea level and high altitude, the intensity of exercise-induced breathlessness increased significantly at high altitude. This was associated with a higher minute ventilation and respiratory frequency for any given exercise level, whereas tidal volume was not significantly altered from sea level values. The increased intensity of breathlessness with exercise did not change significantly over the 5 days at high altitude. These results suggest that the increased intensity of exercise-induced breathlessness at high altitude is not related to peripheral mechanisms or the pattern of ventilation, or to the level of hypoxia per se, but to the level of reflexly increased ventilation.  (+info)

(4/4931) Effect of thoracotomy and lung resection on exercise capacity in patients with lung cancer.

BACKGROUND: Resection is the treatment of choice for lung cancer, but may cause impaired cardiopulmonary function with an adverse effect on quality of life. Few studies have considered the effects of thoracotomy alone on lung function, and whether the operation itself can impair subsequent exercise capacity. METHODS: Patients being considered for lung resection (n = 106) underwent full static and dynamic pulmonary function testing which was repeated 3-6 months after surgery (n = 53). RESULTS: Thoracotomy alone (n = 13) produced a reduction in forced expiratory volume in one second (FEV1; mean (SE) 2.10 (0.16) versus 1.87 (0.15) l; p<0.05). Wedge resection (n = 13) produced a non-significant reduction in total lung capacity (TLC) only. Lobectomy (n = 14) reduced forced vital capacity (FVC), TLC, and carbon monoxide transfer factor but exercise capacity was unchanged. Only pneumonectomy (n = 13) reduced exercise capacity by 28% (PVO2 23.9 (1.5) versus 17.2 (1.7) ml/min/kg; difference (95% CI) 6.72 (3.15 to 10.28); p<0.01) and three patients changed from a cardiac limitation to exercise before pneumonectomy to pulmonary limitation afterwards. CONCLUSIONS: Neither thoracotomy alone nor limited lung resection has a significant effect on exercise capacity. Only pneumonectomy is associated with impaired exercise performance, and then perhaps not as much as might be expected.  (+info)

(5/4931) Pseudo-steroid resistant asthma.

BACKGROUND: Steroid resistant asthma (SRA) represents a small subgroup of those patients who have asthma and who are difficult to manage. Two patients with apparent SRA are described, and 12 additional cases who were admitted to the same hospital are reviewed. METHODS: The subjects were selected from a tertiary hospital setting by review of all asthma patients admitted over a two year period. Subjects were defined as those who failed to respond to high doses of bronchodilators and oral glucocorticosteroids, as judged by subjective assessment, audible wheeze on examination, and serial peak flow measurements. RESULTS: In 11 of the 14 patients identified there was little to substantiate the diagnosis of severe or steroid resistant asthma apart from symptoms and upper respiratory wheeze. Useful tests to differentiate this group of patients from those with severe asthma appear to be: the inability to perform reproducible forced expiratory manoeuvres, normal airway resistance, and a concentration of histamine causing a 20% fall in the forced expiratory volume (FEV1) being within the range for normal subjects (PC20). Of the 14 subjects, four were health care staff and two reported childhood sexual abuse. CONCLUSION: Such patients are important to identify as they require supportive treatment which should not consist of high doses of glucocorticosteroids and beta2 adrenergic agonists. Diagnoses other than asthma, such as gastro-oesophageal reflux, hyperventilation, vocal cord dysfunction and sleep apnoea, should be sought as these may be a cause of glucocorticosteroid treatment failure and pseudo-SRA, and may respond to alternative treatment.  (+info)

(6/4931) Influence of family factors on the incidence of lower respiratory illness during the first year of life.

In a study of a cohort of over 2000 children born between 1963 and 1965, the incidence of bronchitis and pneumonia during their first year of life was found to be associated with several family factors. The most important determinant of respiratory illness in these infants was an attack of bronchitis or pneumonia in a sibling. The age of these siblings, and their number, also contributed to this incidence. Parental respiratory symptoms, including persistent cough and phlegm, and asthma or wheezing, as well as parental smoking habits, had lesser but nevertheless important effects. Parental smoking, however, stands out from all other factors as the one most amenable to change in seeking to prevent bronchitis and pneumonia in infants.  (+info)

(7/4931) Urinary cotinine and exposure to parental smoking in a population of children with asthma.

BACKGROUND: Studies of the effects of tobacco smoke often rely on reported exposure to cigarette smoke, a measure that is subject to bias. We describe here the relationship between parental smoking exposure as assessed by urinary cotinine excretion and lung function in children with asthma. METHODS: We studied 90 children 4-14 years of age, who reported a confirmed diagnosis or symptoms of asthma. In each child, we assessed baseline pulmonary function (spirometry) and bronchial responsiveness to carbachol stimulation. Urinary cotinine was measured by HPLC with ultraviolet detection. RESULTS: Urinary cotinine concentrations in the children were significantly correlated (P <0.001) with the number of cigarettes the parents, especially the mothers, smoked. Bronchial responsiveness to carbachol (but not spirometry test results) was correlated (P <0.03) with urinary cotinine in the children. CONCLUSION: Passive smoke exposure increases the bronchial responsiveness to carbachol in asthmatic children.  (+info)

(8/4931) Fragile lung in the Marfan syndrome.

Two cases of the Marfan syndrome presented with spontaneous pneumothorax. Both had chest radiographs showing bilateral bullae in the upper lung zones and pulmonary function tests consistent with mild emphysema. There were dereases in forced expiratory flow rates at low lung volumes, carbon monoxide transfer factor, and lung elastic recoil. It is suggested that pneumothorax and bullous emphysema in this syndrome are caused by a weakness in the pulmonary connective tissue framework.  (+info)