Single breath nitrogen test as predictor of lung function decline and COPD over an 8-year follow-up.

BACKGROUND: The single breath nitrogen (SBN2) test was proposed for early detection of "small airways disease" in the seventies. Few longitudinal studies have subsequently evaluated the relationships between SBN2 test measurements and lung function decline or COPD incidence. AIM: This study evaluates whether SBN2 test abnormalities may be significant predictors of lung function decline and COPD incidence over an 8-year follow-up. STUDY DESIGN AND METHODS: In this longitudinal study, 907 adults (20+ years old; 56% males) from the prospective Po River Delta epidemiological study underwent SBN2 test at baseline and spirometry testing at both baseline and follow-up 8-year apart. Multinomial and multiple regression models were used to assess associations of SBN2 indexes and rates of FEV1 decline or risk of COPD incidence over time, after adjusting for sex, height and baseline age, FEV1 and smoking status. COPD was defined according to either GOLD or ATS-ERS criteria. RESULTS: Among SBN2 indexes, only the slope of alveolar plateau (N2-slope) was significantly associated with rates of FEV1 decline (7.93 mL/year for a one-unit change in N2-slope, p<0.0001), and with an increased risk of developing COPD as defined by GOLD (RR 1.81, 95%CI 1.29-2.52, mild; RR 2.78, 95%CI 1.70-4.53, moderate or severe obstruction) and ATS-ERS criteria (RR 1.62, 95%CI 1.14-2.29, mild; RR 3.40, 95%CI 1.72-6.73, moderate or severe obstruction). CONCLUSION: In this population-based study, N2-slope from SBN2 test is a significant predictor of lung function decline and COPD incidence over an 8-year follow-up, confirming the role of the "small airways disease" in the natural history of COPD.

Chronic bronchitis before age 50 years predicts incident airflow limitation and mortality risk.

BACKGROUND: Previous studies on the relationship of chronic bronchitis to incident airflow limitation and all-cause mortality have provided conflicting results, with positive findings reported mainly by studies that included populations of young adults. This study sought to determine whether having chronic cough and sputum production in the absence of airflow limitation is associated with onset of airflow limitation, all-cause mortality and serum levels of C-reactive protein (CRP) and interleukin-8 (IL-8), and whether subjects' age influences these relationships. METHODS: 1412 participants in the long-term Tucson Epidemiological Study of Airway Obstructive Disease who at enrolment (1972-1973) were 21-80 years old and had FEV(1)/FVC (forced expiratory volume in 1 s/forced vital capacity) > or = 70% and no asthma were identified. Chronic bronchitis was defined as cough and phlegm production on most days for > or = 3 months in two or more consecutive years. Incidence of airflow limitation was defined as the first follow-up survey with FEV(1)/FVC <70%. Serum IL-8 and CRP levels were measured in cryopreserved samples from the enrolment survey. RESULTS: After adjusting for covariates, chronic bronchitis at enrolment significantly increased the risk for incident airflow limitation and all-cause mortality among subjects <50 years old (HR 2.2, 95% CI 1.3 to 3.8; and HR 2.2, 95% CI 1.3 to 3.8; respectively), but not among subjects > or = 50 years old (HR 0.9, 95% CI 0.6 to 1.4; and HR 1.0, 95% CI 0.7 to 1.3). Chronic bronchitis was associated with increased IL-8 and CRP serum levels only among subjects <50 years old. CONCLUSIONS: Among adults <50 years old, chronic bronchitis unaccompanied by airflow limitation may represent an early marker of susceptibility to the effects of cigarette smoking on systemic inflammation and long-term risk for chronic obstructive pulmonary disease and all-cause mortality.

Association of physical activity and human sleep disorders.

BACKGROUND: It is generally believed that exercise exerts a beneficial effect on the quality of sleep. However, most studies regarding exercise and sleep have been concerned with the influence of exercise on sleep architecture and efficiency, and not on its effects in the prevention and treatment of sleep disorders. Moreover, epidemiological evidence of the benefits of exercise on sleep are limited. OBJECTIVE: To investigate the influence of moderate exercise or physical activity on self-reported sleep disorders among a randomly selected population of adults. SUBJECTS AND METHODS: Study subjects were participants in the Tucson Epidemiological Study of Obstructive Airways Disease who in the 12th survey completed health questionnaires that included several questions on physical exercise and sleep disorders. Sleep disorders were classified as disorders in maintaining sleep, excessive daily sleepiness, nightmares, and any sleep disorder. Six questions regarding exercise and physical activity were asked. Analyses were performed using multivariate logistic regression models with selected measures of sleep disorders as dependent variables and measures of exercise and physical activity as the independent or predictor variables. RESULTS: There were 319 men and 403 women included in the analyses. The results showed that more women than men reported participating in a regular exercise program and having sleep symptoms of disorders in maintaining sleep and nightmares and that more men than women did regular vigorous activity and walking at a brisk pace for more than 6 blocks per day. Both men and women had significantly reduced risk of disorders in maintaining sleep associated with regular activity at least once a week, participating regularly in an exercise program, and walking at a normal pace for more than 6 blocks per day. Reduced risk of any sleep disorder was associated with regular activity at least once a week, and for men, walking at a brisk pace for more than 6 blocks. Among women increases in age also reduced the risk of nightmares. CONCLUSIONS: These data provide additional evidence that a program of regular exercise may be a useful therapeutic modality in the treatment of patients with sleep disorders.

Comparison of preschool vision screening methods in a population with a high prevalence of astigmatism.

PURPOSE: To compare the effectiveness of four methods of screening 3- to 5-year-old children for astigmatism high enough to require spectacle correction. METHODS: Lea Symbols Visual Acuity Screening (LSVAS), MTI Photoscreening (MTIPS), Nidek KM-500 Keratometry Screening (KERS), and Retinomax K-Plus Noncycloplegic Autorefraction Screening (NCARS) were attempted on 379 preschool children who are members of a Native American tribe having a high prevalence of astigmatism that is primarily corneal in origin. The need for spectacle correction was determined by cycloplegic refraction. Receiver Operating Characteristic (ROC) curves were fit, confidence intervals were determined, and area under the curves was compared. RESULTS: Astigmatism > or = 1.00 D was present in the right eye of 47.5% and in the left eye of 48.0% of children. Spectacles were prescribed for children < 48 months of age who had cylinder > or = 2.00 D and children > or = 48 months who had cylinder > or = 1.50 D, with the result that 33% of subjects required spectacles. Area under the ROC curve was 0.98 for NCARS, 0.92 for KERS, 0.78 for MTIPS, and 0.70 for LSVAS, and each of these values differed significantly from the other three (all P < 0.007). Testability was significantly higher for NCARS (99.5%) and KERS (99.7%) than for MTIPS (93.5%) and LSVAS (92.0%). CONCLUSIONS: In a population that included many children with astigmatism, objective, fully automated screening methods (NCARS and KERS) were superior to both visual acuity screening and photoscreening with subjective interpretation in identifying children who had astigmatism requiring spectacle correction.

Ambulatory monitoring of peak expiratory flow. Reproducibility and quality control.

Eighty-five children and 230 adults from a population study performed ambulatory peak flow readings three times a day for 1 to 2 weeks following a home visit. Three peak expiratory flow (PEF) readings were reported for each of 5,809 test sessions. Within each test session, the third maneuver most frequently (40% of the time) gave the highest PEF reading. This did not vary throughout the day. In subgroups of children and women with a history of asthma or asthma symptoms (hereinafter referred to as "asthma"), the first maneuver during the evening test sessions more frequently gave the highest readings. However, maneuver-induced bronchospasm occurred during less than 5% of the test sessions in both subjects with asthma and in other subjects. The within test session PEF reproducibility was good: overall, the highest and second highest reading matched within one division (10 L/min) 73% of the time and within 30 L/min (9% of the reading) 95% of the time. The best reproducibility was noted after the first two days of testing, during evening and bedtime test sessions (vs morning), and in girls and men. In the group with at least 2 weeks of testing, the coefficient of repeatability (CR) for the week-to-week PEF lability index was 10% for healthy adults and 17% for healthy children. As expected, repeatability was not as good for adults with asthma (CR = 17%) and children with asthma (CR = 28%).

Spirometry and maximal respiratory pressure references from healthy Minnesota 65- to 85-year-old women and men.

OBJECTIVE: To obtain spirometry and maximal respiratory pressure (MRP) reference values for elderly persons. DESIGN: Survey. SETTING: General community. PARTICIPANTS: Four hundred seventy-one healthy ambulatory white women and men age 65+ years. METHODS: A stringent spirometry quality assurance program exceeded American Thoracic Society recommendations. A "healthy" subgroup of 176 women and 112 men between the ages of 65- and 85 years were identified by excluding those with conditions that negatively influenced FEV1 in a multiple regression analysis. Reference equations and normal ranges for FEV1, FVC, FEF25-75%, peak flow, and maximal inspiratory and expiratory pressures (MRPs) were determined from the healthy group with good quality maneuvers. RESULTS: Less than 10% of the subjects were unable to perform three acceptable spirometry maneuvers and ten MRP maneuvers. When the age and height corrected FEV1s from this group were compared with other spirometry reference studies, mean values from the women were nearly identical to those from Morris, while these men had substantially lower FEV1 values (by 0.3- to 0.5L) than elderly men in Crapo's study. Mean peak flow was over 20% higher when compared with previous studies, suggesting greater initial expiratory effort by our subjects. The maximal inspiratory pressure (MIP) values were about 20% higher than those reported by the Cardiovascular Health Study, perhaps because five MIP maneuvers were always performed. CONCLUSION: Spirometry and MRP reference values used for elderly patients should come from population studies using similar techniques and with large numbers of subjects over age 65 years.

Rates of decline in lung function among subjects who restart cigarette smoking.

Several studies have demonstrated that smokers who are able to break the habit generally experience reductions in respiratory symptoms and improvement in pulmonary function; however, far less attention has been given to smokers who are unsuccessful in their attempts at quitting. Recent reports have suggested that these subjects (restarters) may have steeper rates of decline in pulmonary function than subjects never attempting to quit smoking. In this study, we compared rates of decline in FEV1 between restarters and subjects who remained current, ex-smokers, or never-smokers throughout the observation period. The results showed that, in both sexes, subjects who attempt to quit the habit and then restart have significantly steeper rates of decline in their FEV1 than subjects who continue smoking uninterrupted. Female restarters also have significantly steeper rates of decline in FEV1 than ex-smokers. These effects were independent of the amount smoked and respiratory diseases.

An 8-year follow-up of carbon monoxide diffusing capacity in a general population sample of northern italy.

STUDY OBJECTIVE: Diffusing capacity of the lung for carbon monoxide (DLCO) is frequently assessed as part of a thorough pulmonary function assessment in patients with pulmonary or cardiopulmonary diseases. However, little information regarding the longitudinal trends of DLCO is available. In this study, we examined the temporal trends in DLCO to determine the effects of smoking and changes in smoking habits. DESIGN: A longitudinal study was recently conducted in the Po River Delta area of northern Italy, in which DLCO measurements were taken approximately 8 years apart in the same subjects; this offered the unique opportunity to assess the temporal changes in DLCO. The longitudinal DLCO data were analyzed independently in two age groups (20 to 40 years, and > or = 40 years) using a repeated-measures analysis. RESULTS: Included were 928 subjects > 20 years old who had DLCO assessments both at baseline and follow-up. Male subjects had higher mean levels of DLCO than female subjects in the older age group (> or = 40 years). Continuous smokers had significantly lower DLCO levels than "never-smokers," but their changes in DLCO during follow-up were the same. This suggests that the lung damage due to smoking had occurred prior to DLCO testing. We also found that the annual decline in DLCO accelerated with age in adults > or = 40 years old. CONCLUSIONS: We conclude that in adults > or = 40 years of age from the general population, DLCO accelerates downwards regardless of gender, smoking, and initial FEV(1) level.

Predictors of oxygen desaturation during submaximal exercise in 8,000 patients.

STUDY OBJECTIVES: To determine predictors of oxygen desaturation during submaximal exercise in patients with various lung diseases. DESIGN AND SETTING: This retrospective case series used pulmonary function laboratory results from all patients referred to a major tertiary-care center. PATIENTS AND MEASUREMENTS: All patients > or = 35 years old who underwent spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), lung volumes, and pulse oximetry during 3-min submaximal step-test exercise during 1996 were included (4,545 men and 3,472 women). Logistic regression models, correcting for gender, age, and weight, determined the odds ratios (ORs) for oxygen desaturation of > or = 4% during exercise for each category of lung function abnormality (compared to those with entirely normal lung function). RESULTS: Approximately 74% of the patients had airways obstruction, while only 5.6% had restriction of lung volumes. One third of those with obstruction had a low DLCO, compared to 56% with restriction, while 2.7% had a low DLCO without obstruction or restriction. The risk of oxygen desaturation during submaximal exercise was very high (OR, 34) in patients with restriction and low DLCO (as in interstitial lung disease) and in patients with obstruction and low DLCO (as in COPD; OR, 18), intermediate (OR, 9) in patients with only a low DLCO, and lowest in those with a normal DLCO (OR, 4 if restricted; OR, 2 if obstructed). A cut point of DLCO < 62% predicted resulted in 75% sensitivity and specificity for exercise desaturation. No untoward cardiac events occurred in any patients during or following the submaximal exercise tests. CONCLUSIONS: The risk of oxygen desaturation during submaximal exercise is very high in patients with a low DLCO. Submaximal exercise tests are safe, even in elderly patients with heart and lung diseases.

Respiratory effects of non-tobacco cigarettes: a longitudinal study in general population.

Data from four consecutive surveys of Tucson longitudinal study of airways obstructive disease were used to examine the relation of respiratory symptoms and pulmonary function to non-tobacco cigarette smoking. The surveys were conducted over a six-year period and provided data on 1802 subjects 15-60 years of age, with a total of 5659 individual questionnaires. Estimated odds ratio (OR) of current non-tobacco smoking for chronic cough was 1.73, for chronic phlegm: 1.53, and for wheeze: 2.01 (p less than 0.05). These estimates were adjusted for age, tobacco smoking and occurrence of the symptom in preceding survey. The increased risk of the symptoms was related to the habit continued for several years, and there was no immediate remission of the symptoms after quitting smoking. A significant (p less than 0.05) reduction in pulmonary function (FEV1, Vmax50 and their ratios with FVC) was found a year or more after current non-tobacco smoking was reported. Although the average consumption of non-tobacco cigarettes, believed to be marijuana smoking, was less than one per day, significant effects were still detectable in both pulmonary function and respiratory symptoms.

On the maximum likelihood estimation of respiratory response slopes.

Several approaches have been suggested for estimating a respiratory response slope when both x and y variables are observed with error. Recently, a maximum likelihood estimate under the assumption of a bivariate normal distribution has been proposed. A method of moments solution yields a slope estimate of y/x as long as the underlying process mean is nonzero. This paper extends the maximum likelihood approach to the case where the process mean is zero. In this case, certain additional error assumptions must be made to yield a unique estimate. These concepts are applied to the problem of estimating an effective lung volume for steady-state breath-to-breath gas exchange data during exercise.

Kinetics of VO2 with impulse and step exercise in humans.

The constancy of the time course (i.e., dynamic linearity) of the O2 uptake (VO2) response to exercise was examined by testing the law of superposition on data from impulse and step work rate forcings. Two impulses (10 s at a 235-W increase above a 25-W base line, I-235; and 5 s at a 475-W increase above a 25-W base line, I-475), four steps (ST) (25-65 W, ST1; 65-105 W, ST2; 25-105 W, ST3; and 25-145 W, ST4), and the corresponding off-transient responses were performed six to eight times by each of five subjects. The integrated area (G) of the VO2 response for I-235 was similar to that of ST1 and ST2 (P greater than 0.05); the I-475 G was significantly greater (P less than 0.05). The time constant of VO2 during the step function on-transient response for the second exponential component was significantly faster for ST1 and significantly slower for I-235 and I-475 than for ST2, ST3, and ST4 (P less than 0.05). However, I-235 and I-475 time constants for VO2 were not different from the ST off-transient values. Attempts to superimpose the integral of the impulse on the ST data showed that the early rapid increase in VO2 in the ST was underpredicted by the impulse and that the impulse response lagged behind the ST at all points before steady state. It can be concluded that VO2 kinetics failed the test of superposition and are therefore described by a nonlinear dynamic system.

Changes in lung mechanics and reactivity with age after viral bronchiolitis in beagle puppies.

We measured changes with growth in lung function and airway reactivity after acute canine parainfluenza virus type 2 (CPI2, n = 5), canine adenovirus type 2 (CAV2, n = 7), and sequential CAV2-CPI2 (n = 6) infections or no infection (controls, n = 6) in beagle puppies (age approximately 79 days). In the CPI2 and CAV2 groups, a lower respiratory illness developed by day 3 postinfection with clinical recovery by day 14. In the CAV2-CPI2 group, puppies were inoculated initially with CAV2 and 12 days later with CPI2. In this group, illness persisted until day 14 after infection with CPI2. Lung resistance (RL), dynamic (Cdyn) and static (Cst) lung compliance, functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured before infection and at periodic intervals until 239 +/- 43 days of age. Lung function data were analyzed using a longitudinal random effects model. In all groups, FRC, Cst, and Cdyn increased with age. In all infected groups, the regression slopes for Cdyn were steeper than in controls. RL decreased linearly with age without group slope differences. Histamine reactivity increased with age, but there were no differences in slope among groups. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation particularly in the CAV2 and CAV2-CPI2 groups. Thus, viral bronchiolitis produces chronic small airways inflammation in beagle puppies and alters the changes in lung function occurring with growth. Histamine reactivity increases with age and is not modified by viral infection.

Epidemiology of chronic obstructive pulmonary disease.

Morbidity and mortality rates for chronic obstructive pulmonary disease (COPD) have been increasing over time. Epidemiologic investigators of COPD have been exploring the reasons for these increases through prevalence surveys and longitudinal studies. This article examines some of the recent findings.

Parental factors affecting respiratory function during the first year of life.

In a prospective, longitudinal, population-based cohort study of familial and environmental influences on the development of wheezing respiratory illness in early childhood, we identified infant length, weight, gender, and exposure to maternal cigarette smoking as significant determinants of lung function during the first year of life. A cohort of 237 infants (106 females: 131 males) was evaluated, and 496 lung function measurements were made between the ages of 1-12 months. Respiratory function was assessed using the rapid thoracic compression technique to obtain maximum expiratory flow at functional residual capacity (V'maxFRC). Parental history of asthma and smoking habits during pregnancy were obtained by questionnaire. Data were analyzed using a longitudinal random effects model. Infants with a parental history of asthma and/or in utero passive smoke exposure were compared to a reference group of infants who had no parental history of asthma and in whom neither parent smoked pre- or postnatally. Boys were found to have a consistently lower V'maxFRC (-21.05 mL.s(-1)) throughout the first year of life in comparison to girls (P < 0.05). Maternal smoking during pregnancy was associated with a lower V'maxFRC in both genders in comparison to unexposed infants (P < 0.05). V'maxFRC was unaffected by parental history of asthma. Gender-specific normative equations for V'maxFRC throughout the first year of life were derived for the infant cohort as a whole and also for subgroups of infants, based on parental asthma and smoking history. We conclude that lung function during the first year of life differs between genders and is adversely affected by in utero passive tobacco smoke exposure. Gender-specific predictive equations for V'maxFRC should be used during infancy.

Astigmatism and Amblyopia among Native American Children (AANAC): design and methods.

The overall goal of the AANAC study is to improve detection of astigmatism and prevention of amblyopia in populations with a high prevalence of astigmatism. To meet this goal, the study will evaluate four methods of screening for astigmatism in preschool children and will assess both the short-term and long-term benefits of early correction of astigmatism in improving acuity and preventing amblyopia. This paper presents an overview of the design and methodology of the AANAC study. Subjects are members of the Tohono O'Odham Nation, a Native American tribe with a high prevalence of astigmatism. Preschool-age children who attend Head Start are screened with four tools: the Marco Nidek KM-500 autokeratometer, the MTI photoscreener, the Nikon Retinomax K-Plus autorefractor, and the Lea Symbols acuity chart. Sensitivity and specificity for detection of significant astigmatism, as measured by a technique that uses both cycloplegic retinoscopy and cycloplegic autorefraction, is determined for each of the four screening tools. Presence of amblyopia is evaluated by measurement of best-corrected recognition acuity and acuity for orthogonal gratings. Spectacles are provided to all 3-year-old children with > or =2.00 diopters (D) of astigmatism and all 4- and 5-year-old children with > or =1.50 D of astigmatism. Persistence of amblyopia after glasses wearing is evaluated by follow-up measurement of best-corrected recognition acuity and acuity for orthogonal gratings, conducted 2-5 months after glasses are prescribed. Long-term effectiveness of early screening and glasses prescription is evaluated through measurement of recognition acuity in two groups of first-grade children: one group who participated in the Head Start program before the intensive vision screening program was initiated, and a second group who participated in the study's Head Start vision screening program.

Using smoothing splines for detecting ventilatory thresholds.

A recently developed nonparametric regression technique, called a polynomial smoothing spline, is presented for detecting the ventilatory threshold (VT) and respiratory compensation (RC) points from gas exchange response data taken during an incremental exercise test. This type of curve fitting has the advantage of not requiring investigators to specify, a priori, the form of the underlying model, as is required with all linear regression techniques. This procedure yields a mathematically optimal fitted curve through the O2 uptake (VO2) vs CO2 output (VCO2) data and estimates of the process' first and second derivatives. A breakpoint or threshold is indicated by an increase in the value of the derivative and a peak in the second derivative. To evaluate this approach we analyzed gas exchange data collected on nine healthy subjects during a ramp exercise test (15 W.min-1) to the limits of tolerance. Utilizing this procedure we detected VT and RC breakpoints in four subjects and only VT breakpoints in the remaining five subjects. Our results and those obtained using the more conventional linear regression method were similar for those subjects whose RC points were detected using the smoothing spline procedure. However, using regression techniques for subjects with low or otherwise undetectable RC breakpoints, the linear regression method yielded less reliable results in our hands.

Continuous oscillation: outcome in critically ill patients.

PURPOSE: To compare turning by an oscillating bed to standard 2-hour turning. Outcomes were survival, length of stay (LOS), duration of mechanical ventilation, and incidence of pneumonia. METHODS: One hundred and three intensive care patients were randomly assigned to standard turning or turning by an oscillating bed. Data, collected at baseline, daily for 7 days, and then three times weekly until study discharge, included demographics, initial Acute Physiology and Chronic Health Evaluation (APACHE II) score, ventilatory/gas exchange parameters, indicators of pneumonia, nursing measures, and chest roentgenograph. RESULTS: There were no significant differences for LOS, duration of ventilation, nor incidence of pneumonia. Higher survival for subjects on the oscillating bed reached borderline significance (P = .056) for subjects with APACHE II greater than or equal to 20. Longitudinal data were analyzed using the random effects model. No differences in ventilatory or gas exchange parameters were identified. Among subjects who developed pneumonia there was a significantly higher respiratory score (nursing acuity scale) for subjects on the oscillating bed. CONCLUSIONS: In selected critically ill patients oscillating therapy may improve survival and improve airway clearance. The frequency and degree of turning needed to prevent complications and improve outcome remains unclear. These newer beds should be used with discrimination so as to not increase hospital costs unnecessarily.

Adverse respiratory effects following overhaul in firefighters.

Overhaul is the stage in which firefighters search for and extinguish possible sources of reignition. It is common practice not to wear respiratory protection during overhaul. Fifty-one firefighters in two groups, 25 without respiratory protection and 26 wearing cartridge respirators, were monitored for exposure to products of combustion and changes in spirometric measurements and lung permeability following overhaul of a structural fire. Testing at baseline and 1 hour after overhaul included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), serum Clara cell protein (CC16), and serum surfactant-associated protein A (SP-A). Overhaul increased CC16 in both groups, indicating increased alveolarcapillary membrane permeability. Contrary to expectations, SP-A increased and FVC and FEV1 decreased in the firefighters wearing cartridge respirators. Changes in FEV1, CC16, and SP-A were associated with concentrations of specific products of combustion or carboxyhemoglobin levels. Firefighter exposures during overhaul have the potential to cause changes in spirometric measurements and lung permeability, and self-contained breathing apparatus should be worn during overhaul to prevent lung injury.