Health in occupants of energy efficient new homes.

UNLABELLED: A prospective telephone-administered questionnaire study in new home occupants compared general and respiratory health at occupancy and 1 year later in two groups. The test group or cases, was 52 R-2000(TM) homes (128 occupants) built to preset and certified criteria for energy efficient ventilation and construction practices. The control group were 53 new homes (149 occupants) built in the same year in the same geographic area and price range. Analyzed by household, case occupants' summative symptom scores improved significantly over the year of occupancy (Wilcoxon rank sum test, P < 0.006). Analysis of variance of individuals' total symptom scores showed a significant effect of the type of house (P < 0.0001), with lower change of scores in case buildings, but not of age or sex. In comparison with control homes, occupants of case homes reported more improvement in throat irritation (P < 0.004), cough (P < 0.002), fatigue (P < 0.009) and irritability (P < 0.002) with the main change in symptom category being from 'sometimes' to 'never'. Further extension of this pilot study is required to determine if these perceived health benefits are reproducible and/or relate to objective indoor air quality measures. PRACTICAL IMPLICATIONS: New occupants of energy efficient homes with heat recovery ventilators report improvement over 1 year in the symptoms of throat irritation, cough, fatigue, and irritability in comparison with control new home occupants. If this pilot study is reproducible and shown to relate to indoor air quality, prospective new home buyers may be interested in obtaining this health information prior to decision making.

Association between ozone and hospitalization for acute respiratory diseases in children less than 2 years of age.

To clarify the health effects of ozone exposure in young children, the authors studied the association between air pollution and hospital admissions for acute respiratory problems in children less than 2 years of age during the 15-year period from 1980 to 1994 in Toronto, Canada. The daily time series of admissions was adjusted for the influences of day of the week, season, and weather. A 35% (95% confidence interval: 19%, 52%) increase in the daily hospitalization rate for respiratory problems was associated with a 5-day moving average of the daily 1-hour maximum ozone concentration of 45 parts per billion, the May-August average value. The ozone effect persisted after adjustment for other ambient air pollutants or weather variables. Ozone was not associated with hospital admissions during the September-April period. Ambient ozone levels in the summertime should be considered a risk factor for respiratory problems in children less than 2 years of age.

Environmental tobacco smoke exposure patterns: a subanalysis of the Canadian Human Time-Activity Pattern Survey.

This subanalysis of the Canadian Human Activity Pattern Survey examines environmental tobacco smoke (ETS) exposure in non-smoking respondents relative to age, sex, socioeconomic status and prevalence of asthma. 2,381 respondents (response rate 64.5%) from Toronto, Vancouver, Edmonton and Saint John completed a 24-hour recall time-activity diary. For each activity and location, respondents were asked, "was there any smoking during the activity?" Among non-smoking adults, youth, children and asthmatics, the rates of ETS exposure were 32%, 34%, 30% and 42% respectively. Regarding the location of exposure, adults reported ETS exposure in various locations (work, bars and restaurants), including home. Children experienced the most exposure at home, primarily between 4 p.m. and midnight. Adults reported ETS mainly in the living room (16%) and vehicles (13%); for children, the living room (22%) and the bedroom (13%) were the most common locations. Determining characteristic time and location patterns for ETS exposure underpins educational strategies to help non-smokers avoid ETS exposure.

A comparison of biomarkers of ozone exposure in human plasma, nasal lavage, and sputum.

We examined ozone-induced upper and lower airway inflammatory responses and the concentrations of hydroxylated salicylate metabolites using nasal lavage fluid and induced sputum, in order to identify noninvasive and sensitive biomarkers for ozone exposure and effects. A time course for plasma concentration of 2, 3-dihydroxybenzoic acid (2,3-DHBA, a salicylate metabolite and an indicator for hydroxyl radical) in response to 0.12 ppm ozone was also studied. Healthy, young, nonsmoking volunteers were given acetylsalicylic acid (ASA, 975 mg) or placebo orally. Subjects were exposed to ozone (0.12 or 0.4 ppm) or filtered air in an environmental chamber for 2 h, while performing intermittent exercise. Blood was collected hourly over a 4-h period. After exposure, nasal lavage fluid was collected, and sputum was induced using hypertonic saline. Results show that in sputum the percentage of neutrophils was significantly higher after the subjects were exposed to 0.4 ppm ozone (p<.05) than after they were exposed to filtered air or 0.12 ppm ozone. The absolute number and the percentage of macrophages were significantly lower at 0.4 ppm ozone than for filtered air control or 0.12 ppm ozone. The percentage of lymphocytes in sputum was also significantly lower at 0.4 ppm ozone than for filtered air control or 0.12 ppm ozone. The sputum cellular responses to ozone were not significantly altered by ASA treatment. In nasal lavage, cell counts and differentials did not change significantly after exposure to ozone in comparison to filtered air control. The cellular data indicate an acute inflammation developed during ozone exposure in the lower respiratory tract. The concentrations of total protein and interleukin-8 and the activity of N-acetyl-beta-D-glucosaminidase (a lysosomal enzyme) in nasal lavage and sputum did not change significantly following exposure to ozone in comparison to filtered air control. Plasma 2,3-DHBA concentration increased significantly following exposure to 0.12 ppm ozone in an exposure-dependent temporal pattern. Salicylate metabolites in nasal lavage fluid and sputum did not increase significantly following exposure to ozone. There was a marked variation of 2,3-DHBA concentrations in airway fluids. Data suggest that plasma 2,3-DHBA is a sensitive marker indicating acute ozone exposure, even at an ozone concentration that causes minimal observable airway effects in healthy subjects.

In vivo salicylate hydroxylation: a potential biomarker for assessing acute ozone exposure and effects in humans.

Ozone is known to yield hydroxyl radical, which may contribute to ozone-mediated lung injury. In the presence of hydroxyl radical, salicylate is hydroxylated to form 2,3-dihydroxybenzoic acid (2,3-DHBA). There is no evidence of enzymatic formation of 2,3-DHBA. We hypothesized that salicylate hydroxylation might be used as a biomarker indicating human exposure to ozone. Healthy, nonsmoking volunteers, 18 to 34 yr of age, were given acetylsalicylic acid (975 mg) or placebo orally 0.5 h before an exposure. Subjects were exposed to ozone (0.12 or 0.4 ppm) or filtered air in an environmental chamber for 2 h, while performing intermittent exercise. Results indicate significant decrements in FVC, FEV1.0, forced expiratory flows at 50% and 75% of FVC, and peak expiratory flow rate, and an increase in airway resistance, after exposure to 0.4 ppm ozone in comparison with air control (p < 0.05). Exposure to 0.4 ppm ozone also resulted in increased symptom numbers and severity (p < 0.05). When subjects were exposed to 0.12 ppm ozone, changes of pulmonary function and symptoms reported were minimal. Plasma concentration of 2,3-DHBA was significantly increased after exposure to 0.12 and 0.4 ppm ozone in comparison with air control (p < 0.05). There was a significant correlation between ozone-induced changes of pulmonary function and normalized salicylate hydroxylation (p < 0.05). The results indicate that exposure to ozone can initiate in vivo production of hydroxyl radical, a potent reactive agent. Salicylate hydroxylation may then serve as a sensitive dosimetric biomarker for ozone exposure, even at subclinical ozone exposure levels.

The Canadian Human Activity Pattern Survey: report of methods and population surveyed.

The assessment of health risk due to environmental contaminants depends upon accurate estimates of the distribution of population exposures. Exposure assessment, in turn, requires information on the time people spend in micro-environments and their activities during periods of exposure. This paper describes preliminary results including study methodology and population sampled in a large Canadian survey of time-activity patterns. A 24-hour diary recall survey was performed in 2381 households (representing a 65% response rate) to describe in detail the timing, location and activity pattern of one household member (the adult or child with the next birthday). Four cities (Toronto, Vancouver, Edmonton and Saint John, NB) and their suburbs were sampled by random-digit dialling over a nine-month period in 1994/1995. Supplemental questionnaires inquiring about sociodemographic information, house and household characteristics and potential exposure to toxins in the air and water were also administered. In general, the results show that respondents spend the majority of their time indoors (88.6%) with smaller proportions of time outdoors (6.1%) and in vehicles (5.3%). Children under the age of 12 spend more time both indoors and outdoors and less time in transit than do adults. The data from this study will be used to define more accurately the exposure of Canadians to a variety of toxins in exposure assessment models and to improve upon the accuracy of risk assessment for a variety of acute and chronic health effects known or suspected to be related to environmental exposures.

Preoperative prediction of pulmonary complications following thoracic surgery.

The ability of preoperative quality-of-life and physiologic variables to predict postoperative complications was tested in 117 consecutive patients undergoing thoracotomy for possible or definite lung cancer. Preoperatively, quality of life was globally assessed by the QLI and Sickness Impact Profile. Dyspnea was assessed by the Clinical Dyspnea Index and a modified Pneumoconiosis Research Unit question. Spirometry and maximal exercise testing were carried out in 115 and 46 subjects, respectively. Thirty-seven percent experienced at least one respiratory complication (eg, pneumonia, atelectasis prompting bronchoscopy, pulmonary embolism). Twofold or greater increases in respiratory complications were associated with current smoking (p < 0.05), cancer as the final pathologic condition (p < 0.10), at least moderate dyspnea (p < 0.10), FEV 1 < 60 percent of predicted (p < 0.05), ventilatory reserve < 25 L (p < 0.05), and VO2max < 1.25 L (p < 0.05). Twofold increases in the incidence of any complication (respiratory, cardiac, etc) were associated with age > or = 75 years (p < 0.05) and cancer as the final pathologic condition (p < 0.05). We conclude that simple historic information (age, smoking status, cancer status, dyspnea) indicates the risk of postoperative morbidity. General quality-of-life measures were not good predictors of morbidity. Our findings corroborate the few studies supporting the value of VO2max and suggest that the usefulness of the ventilatory reserve deserves further attention.

Effects of short-term inhaled budesonide and beclomethasone dipropionate on serum osteocalcin in premenopausal women.

Serum osteocalcin, a marker of bone osteoblast function, has been shown to be sensitive to even low doses of oral glucocorticoids. The effect of 1 wk of inhaled glucocorticoid therapy with budesonide (200 micrograms/puff), beclomethasone dipropionate (250 micrograms/puff), and placebo at two puffs b.i.d. and four puffs b.i.d. on 0900 serum osteocalcin were compared in a double-blind randomized fashion. A two-way repeated-measures analysis of variance showed no main effect of drug or dosage but a significant drug-dose interaction (p = 0.023). Post hoc investigation of this interaction demonstrated that the serum osteocalcin level while taking four puffs b.i.d. (2,000 micrograms) of beclomethasone dipropionate was significantly lower than that of placebo or budesonide at four puffs b.i.d. (1,600 micrograms). These results suggest that at lower doses no acute measurable effect of inhaled glucocorticoids on serum osteocalcin can be appreciated but that at higher doses inhaled beclomethasone dipropionate has a depressant effect on bone osteoblast function.

Nasal CPAP continues to improve sleep-disordered breathing and daytime oxygenation over long-term follow-up of occlusive sleep apnea syndrome.

To assess the effects of long-term nasal continuous positive airway pressure (CPAP) in occlusive sleep apnea syndrome (OSA), 17 patients with severe symptomatic OSA had repeated spirometry, arterial blood gases, and nocturnal polysomnograms off nasal CPAP after 3 to 46 months of treatment with nasal CPAP. Without loss of weight or change in respiratory mechanics, the ventilatory disturbance index fell from a mean of 87 events per hour to 57 events per hour (p < 0.0001), correlating with an improvement in mean nocturnal desaturation with sleep-disordered breathing events (r = 0.54, p = 0.03). Moreover, the daytime PaO2 rose significantly from a mean of 69 mm Hg to a mean of 82 mm Hg (P = 0.0001) at follow-up. The rise in daytime PaO2 was not only due to the alleviation of daytime hypercapnea observed in eight of nine hypercapneic subjects since the P(A-a)O2 gradient also decreased significantly. The improvement in PaO2 correlated significantly with the number of months of CPAP therapy, suggesting a continuing effect over time (r = 0.58, p = 0.015). These results indicate that there is a reversible element of the severity of OSA and suggest a result of nasal CPAP therapy may be to reverse the adverse and time-dependent effects of hypoxemia and sleep fragmentation on ventilatory control in severe OSA.

Hemodynamic effects of nasal CPAP examined by Doppler echocardiography.

The effects of incremental application of nasal continuous positive airway pressure (0 to 15 cm H2O) on heart rate, pulmonary artery pressure, and cardiac index were studied noninvasively by Doppler echocardiography. By two-way analysis of variance within two groups (19 normal volunteers and six sleep apnea patients), no significant effects on heart rate, pulmonary artery pressure, ventricular size, or cardiac index could be found with increasing positive intrathoracic pressures and consequent lung hyperinflation. In subjects with normal cardiac function, nasal CPAP is safe from a hemodynamic viewpoint. This simple, repeatable and noninvasive technique may be used to assess the clinical safety and efficacy of prescribed nasal CPAP on cardiac hemodynamics in individual patients.

Relationship of lung function to severity of osteoporosis in women.

To determine if the severity of osteoporosis and its resultant hyperkyphosis cause measurable impairment of lung function, 74 women referred for osteoporosis evaluation underwent pulmonary function testing. Women with thoracic wedge compression fractures secondary to osteoporosis had significantly lower percent predicted FVC than did those without fractures. In hierarchical regression analysis, after controlling for age and arm span, there was a significant effect on FVC of the degree of hyperkyphosis as measured by Cobb's angle (increment in R2 = 0.14, p less than 0.001). The addition of the number of vertebral fractures to the model was also significant (increment in R2 = 0.06, p less than 0.002), but cortical bone volume, bone mineral density, and smoking status did not significantly improve the model. From one half of subjects tested, a regression equation was generated relating %FVC and the number of thoracic fractures: %FVC = 103.4 - 9.4 x number of fractures. When used to predict lung function impairment in the second half of study subjects, the correlation between measured and %FVC was r = 0.59 (p less than 0.002). Kyphosis and thoracic compression fractures caused by osteoporosis produce modest but predictable declines in vital capacity in women.

A comparison of men and women with occlusive sleep apnea syndrome.

Among 118 patients with occlusive sleep apnea syndrome (OSA), defined as daytime hypersomnolence and an apnea hypopnea index (AHI) greater than ten events/h, 41 women were compared with 77 men. Body mass index, spirometric study, PaO2, PaCO2, and results from nocturnal polysomnography were examined in a two-way analysis of variance (ANOVA) for the effects of sex, age group, and a sex-age group interaction. The age groups examined were above and below 42 years, the breakpoint for menopause in the women. Younger persons tended to be more obese and to have a higher AHI. Both sexes had similar pulmonary function, AHI, and nocturnal desaturation, but women experienced significantly fewer completely occluded breathing events and had apneas of shorter mean and maximum duration than men of similar ages. No effect of menopausal status per se was observed. In OSA patients, differences in upper airway occlusion and apnea duration suggest differences between the sexes in upper airway physiology or respiratory control.

Percutaneous embolotherapy in life-threatening hemoptysis.

Percutaneous embolization of the bronchial arteries to control massive or recurrent hemoptysis has become an accepted procedure, especially in treating patients with chronic pulmonary disease who are poor candidates for lung resection. Nonbronchial systemic collateral arteries and pulmonary arteries may contribute significantly to pulmonary hemorrhage, but embolization of these vessels has not been stressed in recent literature. When embolization of the bronchial artery fails to control hemoptysis, nonbronchial systemic collateral arteries should be embolized. If no systemic collaterals are present, then embolization of segmental pulmonary arteries may prove helpful.

Determinants of hypercapnia in occlusive sleep apnea syndrome.

To assess the relative contributions of age, gender, obesity, pulmonary function, and the severity of sleep-induced respiratory abnormalities to the development of alveolar hypoventilation in patients with occlusive sleep apnea syndrome, prospective data from III patients with occlusive sleep apnea were analyzed by stepwise logistic and multiple regression techniques. The significant variables in a logistic regression model predicting the presence of hypercapnia were daytime arterial oxygen pressure (PaO2; p less than 0.0001) and gender (p less than 0.04), the latter reflecting the higher number of hypercapnic women in our patient population. Multiple regression analysis performed in the hypercapnic group to study the determinants of the severity of elevation of arterial carbon dioxide tension (PaCO2) revealed significant contribution from the PaO2, the apnea-plus-hypopnea index (AHI), and the percent predicted forced vital capacity (r2 = 0.56; p less than 0.0001), whereas in the normocapnic patients, PaCO2 related to PaO2 only. These results suggest that daytime hypoxemia, mechanical impairment of the respiratory system due to obesity or obstructive airway disease (or both), and the severity of sleep-induced respiratory abnormalities as assessed by AHI contribute to the severity of carbon dioxide retention in patients with occlusive sleep apnea in a multifactorial fashion.

Efficacy of pneumococcal vaccine in severe chronic obstructive pulmonary disease.

Although pneumococcal vaccine has been recommended for patients with chronic obstructive pulmonary disease (COPD), its efficacy in this population has not been shown. A double-blind randomized controlled trial of 14-valent pneumococcal vaccine was carried out in 189 men and women aged 40 to 89 years with a clinical diagnosis of COPD and a forced expiratory volume in 1 second of less than 1.5 L. Of the 189, 92 received the vaccine and 97 received saline placebo. In a randomly chosen subsample of those who received the vaccine the mean titres of specific IgG antibody to selected pneumococcal polysaccharide serotypes increased two- to threefold by 4 weeks after vaccination. Over a 2-year period the rates of death, hospital admissions and emergency visits and the mean length of hospital stay were not significantly different in the two groups. Although a protective effect of 14-valent pneumococcal vaccine could not be shown, the small size of the sample and the relatively low follow-up rates preclude firm conclusions about efficacy from these data alone. The elevated antibody levels before vaccination in some of the patients, suggesting prior infection with Diplococcus pneumoniae, may partly explain the findings.

Mycobacterium kansasii: colonization and disease.

Mycobacterium kansasii has a wide range of virulence from fatal disease to infection and colonization. The laboratory report of growth of M. kansasii is often a problem for the clinician and an encumberance for the patient. To determine the difference between patients who had disease from M. kansasii and those from whom it was isolated without causing disease, we compared the records of 70 patients from whom this mycobacterium was isolated. The group with disease was defined as those patients with more than one culture with luxuriant growth and new, compatible symptoms, signs or radiographic changes. Age, sex, occupation, place of birth and residence, past medical history, skin testing, radiographic changes, in vitro antibiotic sensitivities, and the time and source of the isolation were tabulated. The group without compatible disease had only a single isolate and almost never had any new symptom or sign. Patients with disease from M. kansasii were more often male (P less than 0.02) and had more chronic obstructive lung disease (P less than 0.001). Patients without disease more frequently had isolations from laryngeal swabs (P less than 0.001). The cultures of these swabs had less stringent laboratory decontamination. M. kansasii may be a more frequent colonizer of the upper airway than previously thought. Clinicians should use the same rigorous definition of disease caused by M. kansasii as clinical investigators, namely repeated isolations with luxuriant growth in an appropriate host. The laboratory, instead of the clinician, should investigate positive cultures in patients without disease.

Diffusing capacity for carbon monoxide. The effects of different derivations of breathhold time and alveolar volume and of carbon monoxide back pressure on calculated results.

The effect of deriving breathhold time and alveolar volume in different ways and of subtracting the back pressure of carbon monoxide on the calculated diffusing capacity (DLCO) was examined in 398 young adult smokers, ex-smokers, and nonsmokers. Significantly higher values were obtained when the recommendations of the ATS-DLD Epidemiology Standardization Project were followed for calculating breathhold time and alveolar volume, respectively, compared to following those of the ECCS Standardized Lung Function Testing Project. We therefore recommend that in reporting DLCO results, an explicit statement be included on the methods used to calculate both. Significantly higher values for DLCO were also obtained when CO back pressure was taken into account. The magnitude of this effect in smokers makes it difficult not to recommend its inclusion in epidemiologic studies. In clinical laboratories, however, when correction for CO back pressure is omitted, it is unlikely to result in an underestimate of DLCO of more than 5%, even in smokers.

Dynamics of respiratory drive and pressure during NREM sleep in patients with occlusive apneas.

To study the dynamics of respiratory drive and pressure in patients with occlusive apneas, diaphragmatic electromyogram (EMGdi), esophageal pressure (Pes), and genioglossal electromyogram (EMGge) were monitored during nocturnal sleep in five patients. Both EMGs were analyzed as peak moving time average, and Pes was quantitated as the peak inspiratory change from base line. During the ventilatory phase both EMGs decreased proportionally. The decrease in Pes was less than the decrease observed in EMGdi, and Pes generated for a given EMGdi increased during the preapneic phase in spite of the proportional decrease in EMGdi and EMGge during this period. We conclude that negative inspiratory pressures which lead to the passive collapse of oropharyngeal walls are dependent on both respiratory and upper airway muscle activity and that occlusive apneas of non-rapid-eye-movement (NREM) sleep do occur in spite of proportional changes observed in the activity of both muscle groups. The preapneic increase in negative inspiratory pressures generated for a given respiratory muscle activity is most likely due to the decrease in upper airway muscle activity that is associated with an increase in oropharyngeal resistance.

Relationship between pulmonary function and sleep-induced respiratory abnormalities.

The relationships between pulmonary function and sleep-induced respiratory events were studied in 34 consecutive male patients with suspected sleep apnea syndrome. In view of the effects of obstructive airway disease on pulmonary volume and airway resistance (Raw), patients were divided into two groups, those with and those without obstructive airway disease. Percent predicted functional residual capacity (FRC) correlated significantly with the apnea-plus-hypopnea index (AHI) in patients with and without obstructive airway disease (r = -0.62 and p less than 0.01; and r = -0.57 and p less than 0.01, respectively) whereas percent predicted total lung capacity had a significant relationship with AHI only in patients with obstructive airway disease (r = -0.80; p less than 0.001). In patients without such disease, a significant correlation between inspiratory airway conductance (Gaw) and AHI (r = -0.47; p less than 0.05) was also present, while percent predicted FRC and Gaw did not correlate with normalized weight. These findings suggest that decreased pulmonary volume and increased Raw contribute to the severity of sleep-induced respiratory abnormalities in patients with sleep apnea syndrome regardless of the degree of obesity.