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PubMed2005

Radiation damage to the heart enhances early radiation-induced lung function loss.

In many thoracic cancers, the radiation dose that can safely be delivered to the target volume is limited by the tolerance dose of the surrounding lung tissue. It has been hypothesized that irradiation of the heart may be an additional risk factor for the development of early radiation-induced lung morbidity. In the current study, the dependence of lung tolerance dose on heart irradiation is determined. Fifty percent of the rat lungs were irradiated either including or excluding the heart. Proton beams were used to allow very accurate and conformal dose delivery. Lung function toxicity was scored using a breathing rate assay. We confirmed that the tolerance dose for early lung function damage depends not only on the lung region that is irradiated but also that concomitant irradiation of the heart severely reduces the tolerance of the lung. This study for the first time shows that the response of an organ to irradiation does not necessarily depend on the dose distribution in that organ alone.

Animals↗
PubMed2004

Relationships between high-resolution computed tomography, lung function and bacteriology in stable bronchiectasis.

To determine the relationship between high-resolution computed tomography (HRCT) findings, lung function, and bacteriology in bronchiectasis, we conducted a retrospective study of 49 Korean patients with stable bronchiectasis. To quantify the extent and severity of bronchiectasis, we used a CT scoring system consisting of bronchial dilatation, bronchial wall thickening, the number of bronchiectatic segments, the number of bulla, and the number of emphysema segments. The presence of air-fluid levels and lung consolidation were also evaluated. The results of CT scoring, spirometry and sputum culture were analyzed. Patients with cystic bronchiectasis had higher CT score, more dilated lumen and lower forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), and FEV1/FVC than patients with cylindrical bronchiectasis. Patients with mixed ventilatory impairment had larger number of bronchiectatic segments than patients with obstructive ventilatory impairment. CT score and the number of bronchiectatic segments were significantly associated with FVC and FEV1, while CT score and the number of emphysema segments were significantly associated with FEV1/FVC. Twenty-one patients of 49 patients showed a positive sputum culture including 15 cases of Pseudomonas aeruginosa. The CT score was the most important predictor of lung function. The presence of air-fluid levels predicted bacterial colonization.

Adult↗
PubMed2001

Number concentration and size of particles in urban air: effects on spirometric lung function in adult asthmatic subjects.

Daily variations in ambient particulate air pollution are associated with variations in respiratory lung function. It has been suggested that the effects of particulate matter may be due to particles in the ultrafine (0.01-0.1 microm) size range. Because previous studies on ultrafine particles only used self-monitored peak expiratory flow rate (PEFR), we assessed the associations between particle mass and number concentrations in several size ranges measured at a central site and measured (biweekly) spirometric lung function among a group of 54 adult asthmatics (n = 495 measurements). We also compared results to daily morning, afternoon, and evening PEFR measurements done at home (n = 7,672-8,110 measurements). The median (maximum) 24 hr number concentrations were 14,500/cm(3) (46,500/cm(3)) ultrafine particles and 800/cm(3) (2,800/cm(3)) accumulation mode (0.1-1 microm) particles. The median (maximum) mass concentration of PM(2.5) (particulate matter < 2.5 microm) and PM(10) (particulate matter < 10 microm in aerodynamic diameter) were 8.4 microg/m(3) (38.3 microg/m(3)) and 13.5 microg/m(3) (73.7 microg/m(3)), respectively. The number of accumulation mode particles was consistently inversely associated with PEFR in spirometry. Inverse, but nonsignificant, associations were observed with ultrafine particles, and no associations were observed with large particles (PM(10)). Compared to the effect estimates for self-monitored PEFR, the effect estimates for spirometric PEFR tended to be larger. The standard errors were also larger, probably due to the lower number of spirometric measurements. The present results support the need to monitor the particle number and size distributions in urban air in addition to mass.

Adult↗
PubMed1995

Improved lung function by urokinase infusion in canine lung transplantation using non-heart-beating donors.

We evaluated the effect of urokinase on pulmonary microthrombi formation of the donor lung using a canine cadaver left lung allotransplantation model. Donor animals were sacrificed with an intravenous injection of potassium chloride without heparinization and were divided into three groups. In group 1 (n = 6), cadavers were left at room temperature for 1 hour, and lung retrieval was then performed after flushing the lung block with low potassium-dextran-glucose solution. Donor lungs were stored for 3 hours at 8 degrees C. In group 2 (n = 6), donor lungs were treated as in group 1 except that the cadavers were left at room temperature for 2 hours instead of 1 hour before lung retrieval. In group 3 (n = 6), donor lungs were treated as in group 2 except that high-dose urokinase (120,000 IU) was injected into the main pulmonary artery after flushing with low-potassium-dextrose-glucose solution. In all groups after left lung transplantation, the right pulmonary artery was ligated, and recipient animals were followed up for 6 hours after reperfusion. The fibrin degradation product level in the donor lung tissue was also measured. All recipient animals in group 1 survived the 6-hour observation period with excellent gas exchange and stable hemodynamics. Group 3 had significantly better gas exchange than group 2 and similar cardiopulmonary function as group 1. The fibrin degradation product level in the donor lungs before transplantation was significantly higher in group 3 than in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Lung function 12 months following emphysema resection.

OBJECTIVE: To investigate the mechanism of airflow limitation before and 6 and 12 months after targeted emphysematous resection in 10 male patients aged 67 +/- 8 years (mean +/- SD) with very severe COPD undergoing bilateral thoracoscopic stapling techniques. DESIGN: Lung function, including static lung elastic recoil, was measured 2 weeks before and 6 and 12 months after surgery. RESULTS: Twelve months after surgery, there was a significant (p < 0.001) reduction in total lung capacity (TLC), 9.5 +/- 0.3 L (mean +/- SEM) to 8.5 +/- 0.3 L, functional residual capacity, and residual volume. Airway conductance and FEV1, 0.71 +/- 0.1 L (mean +/- SEM) to 0.95 +/- 0.1 L, improved significantly (p < 0.01). Lung elastic recoil increased markedly at TLC from 11.7 +/- 0.7 cm H2O (mean +/- SEM) to 15.0 +/- 1.0 cm H2O (p < 0.01) as did maximum expiratory airflow in every patient. However, when compared with data obtained in each patient at 6 months, lung volumes are significantly increased, and expiratory airflow and lung elastic recoil pressures are significantly reduced (p < or = 0.05). Analysis of maximum expiratory flow-static elastic recoil pressure curve indicates conductance of the S airway segment (Gs) increased from 0.20 +/- 0.03 L/s/cm H2O (mean +/- SEM) to 0.28 +/- 0.04 L/s/cm H2O (p < 0.02), and critical transmural pressure in the collapsible segment (Ptm') decreased from 3.2 +/- 0.2 cm H2O (mean +/- SEM) to 2.5 +/- 0.2 cm H2O (p < 0.01). CONCLUSION: The improvement in maximal expiratory airflow can be attributed primarily to increased lung elastic recoil and its secondary effect on enlarging airway diameter causing increased airway conductance, increased Gs, and decreased Ptm'. The improvement in lung function and elastic recoil peaks at 6 months.

Aged↗
PubMed2001

High-resolution computed tomography scanning in alpha1-antitrypsin deficiency: relationship to lung function and health status.

The development of computed tomography (CT) has enabled emphysema to be assessed noninvasively. Objective quantification of lung density correlates well with lung function in patients with chronic obstructive pulmonary disease and has been shown to be a sensitive tool for monitoring disease progression. In order to determine the clinical impact of changes seen on high-resolution computed tomography (HRCT), the relationship between the objective quantification of emphysema on HRCT, lung function and health status in 111 patients with alpha1-antitrypsin deficiency was examined (PiZ). The degree of HRCT scan abnormality correlated well (p<0.001 for all comparisons) with forced expiratory volume in one second (r = -0.60- -0.75), specific airway conductance (r = -0.67-0.76), residual volume/total lung capacity (r = 0.46-0.58) and transfer factor of the lung for carbon monoxide (r = -0.64- -0.81). In addition, the CT scans correlated (p<0.001) with health status as assessed by the St. George's Respiratory Questionnaire (SGRQ total: r = -0.38-0.50) and the Short-Form health survey (e.g. physical functioning: r = -0.39-0.54). In summary, other workers have shown high-resolution computed tomography to be a sensitive indicator of disease progression. This study confirms the relationship between high-resolution computed tomography and lung physiology, and suggests the relationship is even stronger in patients with predominantly lower zone pan-lobular emphysema than in usual chronic obstructive pulmonary disease. High-resolution computed tomography also relates to patients disability and impairment as defined by health status questionnaires and, therefore, should be considered as an alternative outcome measure particularly in alpha1-antitrypsin deficiency.

Adult↗
PubMedDate not supplied

Relationship between acute ozone responsiveness and chronic loss of lung function in residents of a high-ozone community.

We hypothesized that acute respiratory responsiveness to ozone predicts chronic lung injury from repeated exposure to ozone-containing air pollution. We tested this hypothesis in 164 middle-aged nonsmoking residents of an ozone-polluted community who underwent lung-function measurements during 1986 and 1987 (i.e., time 3). The time-3 study was a follow up of more comprehensive studies conducted in 1977-1978 (time 1) and in 1982-1983 (time 2). In contrast to the apparent rapid (i.e., approximately 60 ml/y) decline in lung-function measurements between times 1 and 2, our subjects showed little change in forced vital capacity (FVC) or forced expired volume in 1 s (FEV1.0) between times 2 and 3, and they experienced a normal decline between times 1 and 3. A subgroup (n = 45) underwent 2-h laboratory ozone exposures to 0.4 ppm ozone, accompanied by intermittent exercise, and they experienced mild acute reductions in FEV1.0 and FVC, but there was little change in bronchial responsiveness to methacholine. Individual acute responses to laboratory ozone were not correlated with individual long-term changes between times 1 and 3. In summary, the results did not support our initial hypothesis, and they did not confirm rapid function decline in nonsmokers chronically exposed to ozone-containing air pollution.

Adult↗
PubMed1993

A new method to determine dose-effect relations for local lung-function changes using correlated SPECT and CT data.

PURPOSE: To determine dose-effect relations for regional lung-function changes after radiotherapy. METHODS: Single Photon Emission Computed Tomography (SPECT) was performed to quantify regional ventilation and perfusion. CT scans were used to calculate the three-dimensional (3-D) dose distribution. Both SPECT and CT scans were performed prior to radiotherapy and 5 months after the start of the treatment. To obtain combined 3-D information on ventilation, perfusion and dose, the SPECT data were correlated with the corresponding CT data. The relative changes in ventilation and perfusion were calculated in each SPECT voxel (voxel size about 6 x 6 x 6 mm) and related to the dose in that voxel. The average relative changes were determined per dose interval of 4 Gy. This procedure was evaluated using the data from five patients treated for Hodgkin's disease with mantle field irradiation with a prescribed total dose of 40-42 Gy. RESULTS: Dose-effect relations for perfusion were observed in all patients, while in four of the five patients, a dose-effect relation was found for ventilation. The maximal uncertainty of the calculated radiation dose was 11%: a difference between the position of the patient during treatment and during CT scanning caused a maximal dose uncertainty of 6%, while the accuracy of the dose calculation algorithm itself was estimated to be within 5%. CONCLUSION: The results indicate that the combined use of SPECT and CT information is an effective method for determining dose-effect relations for regional lung function parameters in each individual patient.

Adolescent↗
PubMed2001

Molecular diagnosis of intermediate and severe alpha(1)-antitrypsin deficiency: MZ individuals with chronic obstructive pulmonary disease may have lower lung function than MM individuals.

BACKGROUND: We tested whether intermediate (MZ, SZ) and severe (ZZ) alpha(1)-antitrypsin deficiency affects lung function in the population at large. METHODS: We performed spirometry [forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC)] and genotyping of 9187 individuals from the adult general population of Copenhagen, Denmark. RESULTS: As expected, the frequencies of individuals with MM, MS, SS, MZ, SZ, and ZZ genotypes were 0.891, 0.054, 0.001, 0.052, 0.001, and 0.001, respectively. Genotype interacted with clinically established chronic obstructive pulmonary disease (COPD) on the percentage of the predicted FEV(1) (P = 0. 004): the percentage of the predicted FEV(1) was reduced in MZ compared with MM individuals among those with clinically established COPD, but not among those without COPD. Furthermore, SZ compound heterozygotes had lower FEV(1)/FVC ratios than MM individuals (P <0.05), and ZZ homozygotes had lower percentages of the predicted FEV(1) and FEV(1)/FVC ratios than MM, MS, SS, and MZ individuals (all Ps <0.01). Reduced lung function in SZ and ZZ vs MM individuals could be demonstrated in current and ex-smokers, but not in nonsmokers. Compared with MM individuals in the same groups, FEV(1) was reduced 655 mL in MZ individuals with clinically established COPD, 364 mL in SZ current smokers, and 791 mL in ZZ current smokers. CONCLUSIONS: In the population at large, MZ was associated with reduced pulmonary function in individuals with clinically established COPD, whereas SZ and ZZ were associated with reduced pulmonary function in smokers. The presence of the alpha(1)-antitrypsin MZ genotype may in certain circumstances produce marked aggravation of airway obstruction in individuals prone to develop COPD.

Adult↗
PubMed1999

Location of airway inflammation in asthma and the relationship to circadian change in lung function.

Nocturnal asthma is an important part of asthma as the majority of patients with asthma have nocturnal worsening in lung function. The etiology of this process is multifactorial and interactive. There are many naturally occurring circadian rhythms, which for the normal individual have only a minor effect on lung function. However, in the asthmatic patient, these day-to-night alterations produce increased airway inflammation and worsening of asthma. Although asthma is considered an airway disease, the location of the inflammatory response may be greater in the alveolar tissue area. If correct, this could alter the therapeutic approach to this disease.

Airway Resistance↗
PubMed1990

An M1-selective muscarinic receptor antagonist telenzepine improves lung function in patients with chronic obstructive bronchitis.

The effect of an M1-selective muscarinic receptor antagonist telenzepine on lung function was investigated in 18 patients with chronic obstructive bronchitis in a double blind, placebo-controlled, randomized crossover study. FEV1, FEF50, PEF and FVC were measured every 0.5 h up to 2 h, then every 1 h up to 6 h after administration of a single, oral dose of 5 mg in the morning. Compared with placebo, telenzepine increased (time average over 6 hours; median and 68%-range): 1) FEV1 from 1.46 (0.81, 2.06) to 1.67 (1.06, 2.40) l, p less than 0.01; 2) PEF from 3.58 (2.33, 4.55) to 3.88 (3.10, 5.07) l/s, p less than 0.01; 3) FEF50 from 0.93 (0.45, 1.58) to 1.17 (0.67, 1.90) l/s, p less than 0.001. Whereas the median increase in FEV1 15 min after 2 puffs of salbutamol was 20% (range 15 to 74%), FEV1 improved by 32% (range -15 to 130%) at the time of maximum difference between placebo and telenzepine. The heart rate did not change. We conclude that in patients with chronic obstructive bronchitis substantial improvement of lung function parameters can be achieved by an M1-receptor antagonist. It is possible that with the dose administered direct actions on muscarinic receptors on the smooth muscle (M3) contribute to the observed bronchodilatation. The unchanged heart rate indicates little effect on cardiac M2-receptors.

Administration, Oral↗
PubMed1987

Influence of cigarette smoking on lung function at baseline and at follow-up in 14 years: the Framingham Study.

Cross-sectional and prospective associations between lung function and potential determinants were examined in the Framingham Study. Personal characteristics of interest were body height and weight, hand grip strength, smoking habits, history of respiratory symptoms and disease, and hematocrit. Baseline pulmonary function was the most powerful indicator of future FEV1, and cigarette smoking was the most important correctable influence. In addition to baseline FEV1, FVC and smoking habits, the important predictors of future lung function were age, relative weight, respiratory symptoms and hematocrit. There was a higher follow-up FEV1 in those who quit smoking compared to those who continued even after adjustment for other associated variables. Relative weight and hematocrit were associated with FEV1 measured 14 years after baseline (directly for relative weight and inversely for hematocrit).

Adult↗
PubMed2005

Persistence of lung function abnormalities despite sustained success of percutaneous mitral valvotomy: the need for an early indication.

AIMS: We assessed early and long-term pulmonary function changes after percutaneous balloon mitral valvotomy (PBMV). METHODS AND RESULTS: Mitral area, lung function, and exercise capacity were evaluated before, immediately after, and 3 months, 6 months, and 12 months after successful PBMV in 24 patients. PBMV resulted in a significant and sustained increase in mitral area, from 1.0 +/- 0.1 to 1.9 +/- 0.1 cm2 (p = 0.001) [mean +/- SD], with a progressive increase in exercise tolerance at 6-month follow-up (from 22.6 +/- 1.4 to 28.2 +/- 1.2 mL/kg, p = 0.0001). An immediate drop in the diffusing capacity of the lung for carbon monoxide (DLCO) was observed (from 26.7 +/- 1.5 to 22.3 +/- 1.1 mL/min/mm Hg, p = 0.0002) after PBMV, followed by a gradual regression to baseline values at 3 months; at 1 year, the DLCO remained elevated (27.3 +/- 6.3 mL/min/mm Hg). The flow in the small airways was reduced at baseline, and there was no significant change during follow-up. CONCLUSIONS: PBMV produces an initial decrease in DLCO, suggesting a reduction of pulmonary congestion. During follow-up, the regression to the initial lung diffusion values despite a sustained hemodynamic improvement suggests that some irreversible interstitial changes were present. In patients with mitral stenosis, an impairment of lung function parameters suggests that PBMV must be performed early, even if patients have few symptoms.

Adult↗
PubMed1990

Effect of exposures to ambient ozone on ventilatory lung function in children.

This study was undertaken to determine if the ventilatory capacity of children is affected by hourly concentrations of ozone inhaled during their daily activity. Over a 3-wk period (June-July 1987) children who were attending a summer camp in the San Bernardino mountains of California performed spirometry up to three times per day during their stay at the camp. A total of 43 children were tested a total of 461 times. Ozone, oxides of nitrogen, sulfur dioxide, temperature, and relative humidity were measured continuously. Daily average measurements of total suspended particulate and the PM10 particulate fraction (less than or equal to 10 microns) were also made. Hourly ozone concentrations at the time of testing varied between 20 and 245 ppb. Regressions of each individual's FEV1 and FVC supported the view that high ozone levels reduced these lung function parameters. The average regression coefficient for FEV1 on ozone was -0.39 ml/ppb (SEM = 0.12) and for FVC -0.44 ml/ppb (SEM = 0.15), both of which were significantly different from zero. Statistical allowance for temperature and humidity increased the magnitude of these slopes. Nitrogen dioxide never exceeded 40 ppb during the time of testing and averaged 13 ppb. Sulfur dioxide's highest measurement was 8 ppb and often was at the limit of detection. Neither NO2 nor SO2 was considered in the statistical modeling. Data were divided based on whether each subject had been exposed to levels of ozone in excess of the National Ambient Air Quality Standard (NAAQS) during the several hours previous to being tested. Exposures exceeding the NAAQS indicated a significant negative relationship between ozone and FEV1, FVC, and PEFR. Data for nonexceedance periods did not indicate this negative relationship for any of the three lung function parameters, but it could not be determined if this was due to an absence of an ozone effect or to a combination of the increased variability and decreased size of this data subset. These data indicate that lung function changes on a daily basis relate in a negative fashion to ambient ozone levels. The magnitude of the changes are small and are reversed as ambient ozone decreases.

Air Pollutants↗
PubMed2006

Do changes in lung function predict high-altitude pulmonary edema at an early stage?

PURPOSE: Ascent to high altitude is associated with alterations in lung function. The mechanisms of these changes and whether they reflect early stages of high-altitude pulmonary edema (HAPE) has been debated. Therefore, we investigated the time course of pulmonary function in relation to hemodynamics and clinical symptoms in mountaineers ascending rapidly to high altitude. METHODS: In 26 unacclimatized subjects we assessed spirometry, single-breath nitrogen washout, diffusing capacity (DLCO), and Doppler echocardiography in Zurich, 490 m, after climbing within 24 h to Monte Rosa, 4559 m, and after one night at 4559 m. RESULTS: Mean (+/- SD) FVC fell from 103 +/- 9% predicted in Zurich to 96 +/- 10% predicted at 4559 m, FEV1/FVC increased from 0.82 +/- 0.06 to 0.84 +/- 0.08, and closing volume increased from 0.35 +/- 0.14 to 0.44 +/- 0.11 L above residual volume (P < 0.05, all changes). On the following day at 4559 m, closing volume remained elevated in 9 of 21 subjects who had a lower DLCO but similar pulmonary artery systolic pressures compared with the remaining 12 subjects (40 +/- 8 vs 43 +/- 7 mm Hg, P = NS). None of the subjects had overt HAPE. CONCLUSION: We conclude that changes in pulmonary function after rapid ascent to high altitude were consistent with interstitial fluid accumulation, but they were not related to changes in pulmonary artery pressure. Individual lung function responses to high-altitude exposure varied largely and did not predict subsequent HAPE.

Adolescent↗
PubMed1987

Radiological progression and lung function in silicosis: a ten year follow up study.

Chest radiographs and spirometric tests were performed on 81 patients who had silicosis from two granite quarries in 1975, 73 of whom were followed up for two to 10 (mean 7.2) years. Each patient's initial and most recent chest radiographs were assessed independently by three experienced readers, and the yearly declines in forced expiratory volume in one second and forced vital capacity were estimated from two to four (mean 3.45) serial spirometric readings. Estimates of individual dust exposure were based on extensive historical data on hygiene. All but 11 patients were no longer exposed to dust by the start of follow up, but 24 (45%) of 53 patients who had simple silicosis and 11 (55%) of 20 who had the complicated disease showed radiological evidence of disease progression. In patients who had simple silicosis and showed no radiological progression the yearly declines in forced expiratory volume in one second and forced vital capacity were modest (64 ml/year and 59 ml/year, respectively), whereas significantly greater declines in lung function were seen in those who showed radiological evidence of progression (97 ml/year and 95 ml/year, respectively). In addition to radiological progression the previous average dust concentration to which patients had been exposed also influenced declines in both forced expiratory volume in one second and forced vital capacity after allowing for the effects of age, smoking, duration of exposure, history of tuberculosis, initial state of disease, and baseline lung function. The probability of radiological progression was most strongly influenced by the average dust concentration previously exposed to. The progression of simple silicosis is thus accompanied by appreciable declines in lung function and is strongly affected by previous levels of exposure to dust.

Dust↗
PubMed1977

Comparison of different kinds of tests in the evaluation of lung function among healthy smokers and nonsmokers.

The following groups of lung function tests were performed on 25 healthy male smokers and 25 healthy male nonsmokers. 1) Dynamic function tests: PEF, MMEF, and FEV1/FVC %. 2) Static lung volumes: VC, TLC, FRC, FRC/TLC, and RV/TLC. 3) deltaPco2 was used as a measure of ventilation-perfusion inequalities 4) diffusing capacity was measured with the steady state method described by Filley and coworkers. 5) The blood THb and Tbv were measured. One-way analysis of variance showed that PEF, FEV1/FVC %, and MMEF% were lower (p less than 0.05) in the smoking group. Smokers did not differ from nonsmokers with respect to lung volumes. deltaPco2, THb, and TBV were higher and diffusing capacity lower in the smoking group (p less than 0.001).

Adult↗