Pulmonary Function Laboratory Research Articles

Aging does not affect beta-agonist responsiveness after methacholine-induced bronchoconstriction.

To assess the response to an inhaled beta-agonist alone or in combination with an anticholinergic agent after methacholine-induced bronchoconstriction in four age groups. Retrospective analysis. Pulmonary function laboratory in a university-affiliated hospital. Seven hundred sixty-four consecutive subjects with a 20% reduction or more in forced expiratory volume during the first second (FEV1) of exhalation from total lung capacity after inhaling 189 or fewer cumulative units of methacholine were included in the analysis. The first 382 subjects received three inhalations of metaproterenol (total of 1.95 mg), and the other 382 subjects received three inhalations of albuterol and ipratropium combination (total of 309 microg of albuterol and 54 microg of ipratropium) after methacholine-induced bronchoconstriction. The response to bronchodilators was assessed as the postbronchodilator percentage change in FEV1 and the percentage of subjects recovering to 90% or better of baseline FEV1 after the use of bronchodilator. The percentage change in FEV1 postbronchodilator in the elderly was similar to that of the younger subjects. The percentage of subjects who recovered to 90% or better of their baseline FEV1 postbronchodilator was also similar in the elderly and younger age groups. Response to metaproterenol was similar to that of the albuterol/ipratropium combination in all age groups (all P>.05). Aging does not affect bronchodilator response to beta-agonist after methacholine-induced bronchoconstriction. The responsiveness to beta-agonist alone is similar to the responsiveness to the combination of beta-agonist and anticholinergic agent in all age groups.

Repeatability of spirometry in 18,000 adult patients.

The objective of this study was to determine the limits for repeatability of FEV1, FVC, and PEF during spirometry test sessions in adult outpatients. A retrospective chart review of 18,000 consecutive patients, aged 20 to 90 years, referred to a large outpatient pulmonary function laboratory for testing was performed. Measurements included the differences between the highest and second-highest FVC (dFVC), FEV1 (dFEV1), and PEF (dPEF), from prebronchodilator spirometry, and anthropometric factors. Ninety percent of the patients were able to reproduce FEV1 within 120 ml (6.1%), FVC within 150 ml (5.3%), and PEF within 0.80 L (12%). Patient characteristics, such as sex, age, height, smoking status, and FEV1 (% predicted), had very little effect on repeatability, explaining only 2 to 4% of the variation in repeatability (expressed in milliliters). We conclude that the ability of patients to meet or exceed spirometry repeatability goals does not depend on patient characteristics when testing is performed by experienced personnel. The current American Thoracic Society repeatability goal of 200 ml for FEV1 and FVC may be too lenient.

Diagnostic Value of Negative Expiratory Pressure for Airway Hyperreactivity

To examine the value of negative expiratory pressure (NEP) in the assessment of methacholine bronchoprovocation testing (BPT). Prospective, observational study. Pulmonary function laboratory in a university hospital. Fifty-nine patients with chronic cough referred from outpatient clinics for methacholine BPT. Each subject inhaled successive doubling concentrations of methacholine (from 0.049 to 25 mg/mL) until the FEV(1) decreased for > 20% or the maximum concentration of methacholine was inhaled. NEP was measured in the sitting position during tidal breathing before and after methacholine BPT. The FEV(1) and forced oscillation airway resistance (Rrs) and interrupter airway resistance (Rint) were also obtained simultaneously. A positive BPT result was defined as a fall in FEV(1) > or = 20%. At baseline, only five patients had expiratory flow limitation as demonstrated by NEP (EFL-N). There were 39 patients with positive BPT results, and the other 20 patients had negative results. Among the BPT-positive patients, only 13 patients (33.3%) had EFL-N after methacholine challenge. The sensitivity indexes (absolute change/SD) of FEV(1), NEP, Rrs, and Rint were 16.0 +/- 9.6%, 1.1 +/- 1.6%, 3.8 +/- 4.5%, and 5.89 +/- 4.4% (mean +/- SD), respectively. The percentage changes in FEV(1) in BPT-positive patients correlated with the percentage changes in Rrs (r = 0.419, p = 0.008) and only marginally with the percentage changes in Rint (r = 0.307, p = 0.058), but not with the changes in EFL-N (r = 0.048, p = 0.77). These data suggest that NEP at sitting position is not sensitive in the assessment of methacholine bronchoprovocation as compared to FEV(1) and airway resistance measurements.

Historical review: the carbon monoxide diffusing capacity (DLCO) and its membrane (DM) and red cell (Theta.Vc) components.

The single breath carbon monoxide diffusing capacity (DLCO sb), also called the transfer factor (TLCO), was introduced by Marie and August Krogh in two papers (Krogh and Krogh, Skand. Arch. Physiol. 23, 236-247, 1909; Krogh, J. Physiol., Lond. 49, 271-296, 1915). Physiologically, their measurements showed that sufficient oxygen (by extrapolation from CO) diffused passively from gas to blood without the need to postulate oxygen secretion, a popular theory at the time. Their DLCO sb technique was neglected until the advent of the infra-red CO meter in the 1950s. Ogilvie et al., J. Clin. Invest. 36, 1-17, 1957 published a standardized technique for a 'modified Krogh' single breath DLCO, which eventually became the method of choice in pulmonary function laboratories. The Roughton-Forster equation (J. Appl. Physiol. 1957, 11, 290-302) was an important step conceptually; it partitioned alveolar-capillary diffusion of oxygen (O2) and carbon monoxide (CO) into a membrane component (DM) and a red cell component (theta.Vc) where theta is the DLCO (or DL(O2)) per ml of blood (measured in vitro), and Vc is the pulmonary capillary volume. This equation was based on the kinetics of O2 and CO with haemoglobin (Hb) in solution and with whole blood Hartridge and Roughton, Nature, 1923, 111, 325-326; Proc. R. Soc. Lond. Ser. A, 1923, 104, 376-394; (Proc. R. Soc. Lond. Ser. B, 1923, 94, 336-367; Proc. R. Soc. Lond. Ser. A 1923, 104, 395-430; J. Physiol., Lond. 1927, 62, 232-242; Roughton, Proc. R. Soc. Lond. Ser. B 1932, 111, 1-36) and on the relationship between alveolar P(O2) and 1/DLCO. Subsequently, the relationship between DL(O2) (Lilienthal et al., Am. J. Physiol. 147, 199-216, 1946) and DL(CO) was defined. More recently, the measurement of the nitric oxide diffusing capacity (DLNO) has been introduced. For DL(O2) and DLNO the membrane component (as 1/DM) is an important part of the overall diffusion (transfer) resistance. For the DLCO, 1/theta.Vc probably plays the greater role as the rate limiting step. A crucial question, the effect of unstirred plasma layers on the 'true' value of thetaCO in vivo, has not been resolved, but this does not detract from the clinical role of the DLCO sb (TLCO) as an essential test of lung function.

Body Composition and Resting Energy Expenditure in Clinically Stable, Non–Weight-Losing Patients With Severe Emphysema

To characterize the metabolic status of weight-stable and clinically stable individuals with advanced emphysema. Seventy-nine patients with severe emphysema (FEV(1), 29 +/- 13% of predicted [mean +/- SD]) evaluated for enrollment in the National Emphysema Treatment Trial and 20 age-matched healthy subjects were studied. Pulmonary function laboratory of university-affiliated teaching hospital. Data collection. We measured lung function, body composition, serum leptin levels, serum tumor necrosis factor receptors (sTNF-Rs), resting oxygen consumption (RVO(2)) normalized to weight in kilograms (RVO(2)/kg), and RVO(2) normalized to fat-free mass (FFM) [RVO(2)/FFM]. The patient group and healthy group had similar age, body mass index (BMI), and body composition. RVO(2)/kg, RVO(2)/FFM, and sTNF-R levels were higher in patients compared to healthy subjects. There were no differences in serum leptin levels between emphysematous and healthy subjects, and there was no correlation between leptin and sTNF-R and RVO(2)/kg. Furthermore, both groups had similar gender-related differences in FFM, percentage of body fat, and serum leptin levels. Patients with lower BMI showed the greatest differences from control subjects in RVO(2)/kg. In weight-stable subjects with advanced emphysema, RVO(2)/kg and RVO(2)/FFM were higher compared to healthy subjects, especially in those with BMI in the lower end of the normal range. RVO(2)/kg and RVO(2)/FFM did not correlate with leptin or sTNF-R levels. These data show that a higher metabolic rate is found in patients with emphysema who are clinically and weight stable. Thus, hypermetabolism is a feature of the disease and not sufficient to lead to weight loss.

Ratio Between Forced Expiratory Flow Between 25% and 75% of Vital Capacity and FVC Is a Determinant of Airway Reactivity and Sensitivity to Methacholine

The ratio between forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75)) and FVC is thought to reflect dysanapsis between airway size and lung size. A low FEF(25-75)/FVC ratio is associated with airway responsiveness to methacholine in middle-aged and older men. The current study was designed to assess this relationship in both male and female subjects over a broader range of ages. Data analysis of consecutive subjects who had a >or= 20% reduction in FEV(1) after <or= 189 cumulative units of methacholine over a 7-year period. Pulmonary function laboratory in a university-affiliated hospital. A total of 764 consecutive subjects aged 4 to 91 years (mean +/- SD age, 40.8 +/- 19.6 years). There were 223 male (29.3%) and 540 female (70.7%) subjects. Airway reactivity was assessed as the dose-response slope of the reduction in FEV(1) from baseline vs the cumulative dose of inhaled methacholine. The cumulative dose of methacholine causing 20% reduction in FEV(1) (PD(20)) was used as the indicator of airway sensitivity. In a linear regression model that included age, height, and percentage of predicted FEV(1), the FEF(25-75)/FVC ratio accounted for 7.6% of variability in airway reactivity (p < 0.0001, r(2) = 0.076). Subjects with higher airway sensitivity, indicated by lower PD(20), also had a lower FEF(25-75)/FVC ratio. A low FEF(25-75)/FVC ratio, indicating small airway size relative to lung size, is associated with higher airway sensitivity and reactivity to methacholine in susceptible subjects.

A Spirometry-Based Algorithm To Direct Lung Function Testing in the Pulmonary Function Laboratory

To design a spirometry-based algorithm to predict pulmonary restrictive impairment and reduce the number of patients undergoing unnecessary lung volume testing. Two prospective studies of 259 consecutive patients and 265 consecutive patients used to derive and validate the algorithm, respectively. A pulmonary function laboratory of a tertiary care hospital. Consecutive adults referred to the laboratory for lung volume measurements and spirometry. The sensitivity of the algorithm for predicting pulmonary restriction and the cost savings associated with its use. Total lung capacity correlated strongly with FVC (r = 0.66) and showed an inverse correlation with the FEV(1)/FVC ratio (r = - 0.41). According to the algorithm, only patients with an FVC < 85% of predicted and an FEV(1)/FVC ratio >or= 55% required lung volume measurements following spirometry. The algorithm had a high sensitivity for predicting restriction and a high negative predictive value (NPV) for excluding restriction (sensitivity, 96%; NPV, 98%). The diagnostic properties of the algorithm were reproducible in the validation study. Application of the algorithm would eliminate the need for lung volume testing in 48 to 49% of patients referred to the pulmonary function test (PFT) laboratory, reducing costs by 33%. A spirometry-based algorithm accurately excludes pulmonary restriction and reduces unnecessary lung volume testing in the PFT laboratory almost in half.

Measurement Variability in Single-Breath Diffusing Capacity of the Lung

The single-breath diffusing capacity of the lung (DLCO) is a commonly performed pulmonary function test. The current American Thoracic Society (ATS) recommendations for reproducibility of DLCO measurements suggest that two measurements for the DLCO agree within 10% or 3 mL/min/mm Hg of the average value. The European Respiratory Society (ERS) recommends that two measurements should agree within 10%. The objectives of the present study were to examine whether the current reproducibility criteria were met in a general pulmonary function laboratory and to determine whether alternative criteria might be appropriate. Cross-sectional study. University-based pulmonary function laboratory. Patients referred for spirometry, helium lung volumes, and DLCO measurement. None. In a sample of 6,193 patients referred for clinical testing, 98.3% had two DLCO values that fulfilled the current ATS criteria for reproducibility. The coefficient of variation (CV) and the percentage difference between two repeat measurements were inversely associated with the baseline DLCO and the FEV(1). As the baseline DLCO (percentage of predicted) or FEV(1) (percentage of predicted) decreased, there was an increase in the CV and the percentage difference. In contrast, the absolute difference between repeat measurements was relatively stable irrespective of the baseline DLCO or FEV(1) values. Other patient factors, such as gender and race, were not associated with measurement variability. Using an absolute difference of 2 to 2.5 mL/min/mm Hg between two DLCO measurements as alternative criteria for reproducibility, 91.5% and 95.8% of the patient sample fulfilled these criteria, respectively. Reproducibility of the DLCO measurement is generally much better than current standards allow. Future standards should consider an absolute difference rather than a percentage difference criterion for DLCO reproducibility.

The effect of inhaled β2-agonists on clinical outcomes in chronic obstructive pulmonary disease

The major clinical outcomes measured in evaluating the responses to pharmacotherapy in patients with chronic obstructive pulmonary disease (COPD) include the severity of dyspnea, exercise capacity, exacerbations, and health status. Various studies have demonstrated that testing for acute bronchodilator reversibility in the pulmonary function laboratory does not predict the clinical responses to a trial of bronchodilator therapy in patients with COPD. Separate studies have shown that inhaled albuterol, both a single dose (300 microg) and 2 weeks of therapy (200 microg/4x/day), reduces dyspnea. There is more published information available about the effects of long-acting (>/=12 hours' duration of action) inhaled beta(2)-agonists because of greater interest in considering clinical outcomes at the time of drug testing. In one randomized clinical trial, formoterol reduced symptoms (as recorded in a home diary) and improved health status. Nine clinical studies have examined the effects of salmeterol on clinical outcomes. Salmeterol reduced the perception of breathlessness (in 6 of 9 studies) and improved health status (in 3 of 4 studies). These results collectively demonstrate that long-acting inhaled beta(2)-agonists not only relax bronchial smooth muscle but also provide important clinical benefits in symptomatic patients with COPD.

Accuracy of spirometry in general practice. results of an evaluation study in patients with chronic obstructive pulmonary disease (COPD)

Background:At this time, many general practices in the Netherlands have their own spirometer. However, there are indications in the literature that spirometry performed in the general practice setting may be inaccurate.Aims:To compare FEV1 and FVC values obtained in general practice to a ‘gold standard', i.e. the same parameters obtained in a pulmonary function laboratory by an experienced lung function technician.Methods:General practitioners and practice assistants from 61 Dutch general practices were trained to perform spirometry. Subsequently, these practices recruited patients with COPD for study participation. For each patient, pre- and post-bronchodilator (BD) FEV1 and FVC values were first assessed in a pulmonary function laboratory and within a few days again in the patients' own general practice. The same type of spirometer (Microloop II, MicroMedical Ltd.) and spirometry software (Spirare, Diagnostica Ltd.) was used in all practices as well as in the pulmonary function laboratory.Results: Pairs of spirometric tests were available for 299 patients. (197 males, mean age 59.2 [SD 9.6], mean FEV1 % predicted 62.8 [SD 17.6]). Pre-BD FEV1 was on average 79 ml (95% CI 55, 103) and FVC 99 ml (95% CI 54, 143) higher for the general practice measurements. For post-BD measurements, FEV1 was 61 ml (95% CI 39, 84) and FVC 49 ml (95% CI 3, 95) higher, also in favour of the general practice measurements.Conclusion:Relevant spirometric values (FEV1, FVC) obtained in general practice appear to be equivalent to values obtained in a pulmonary function laboratory. Further analyses of our data are required to eliminate possible alternative explanations for this rather unexpected finding.

Tidal Volume and Respiratory Timing Derived From a Portable Ventilation Monitor

To determine the accuracy of a portable magnetometer designed to measure tidal volume (VT), inspiratory time (TI), and expiratory time (TE). Fourteen healthy subjects. Subjects breathed over a sixfold range of VTs while at rest (sitting and standing) and during treadmill exercise. We then compared VT, TI, and TE measured by magnetometry (VTmag, TImag, and TEmag) with VT, TI, and TE measured by spirometry (VTspiro, TIspiro, and TEspiro, respectively). Pulmonary function and exercise physiology laboratories. The sternal-umbilical distance and the anteroposterior displacements of the rib cage and abdomen were measured with two pairs of magnetometer coils. VT was calculated from the sum of these three signals, and was simultaneously measured using a spirometer or flow meter. A total of 1,111 breaths were analyzed for the resting condition, and 1,163 breaths were analyzed for the exercise condition. We found that VTmag was highly correlated with VTspiro at rest (R2 = 0.90) and during exercise (R2 = 0.79) for pooled data. The slope of this relationship approached the line of identity. The mean percentage differences between VTmag and VTspiro were 10.1 +/- 6.6% at rest and 13.5 +/- 8.6% with exercise. By Bland-Altman analysis, the mean differences between VTmag and VTspiro were 38 mL at rest with changes in posture, and 182 mL during exercise. TImag and TIspiro values and TEmag and TEspiro values also were highly correlated (R2 = 0.97 and R2 = 0.95, respectively) for pooled data. A portable magnetometer system can give useful measures of VT, TI, and TE over a wide range of VTs in sitting, standing, and exercising subjects.

Effect of a Nonrebreathing Exhalation Valve on Long-term Nasal Ventilation Using a Bilevel Device

To determine whether an exhalation valve designed to minimize rebreathing improves daytime or nocturnal gas exchange or improves symptoms compared with a traditional valve during nocturnal nasal ventilation delivered using a bilevel pressure ventilation device. Prospective direct comparison trial with each patient sequentially using both valves, during a 2-week run-in period with a traditional valve, a 2-week trial with the nonrebreathing valve, and a 2-week washout period with the traditional valve. Outpatient pulmonary function laboratory and home nocturnal monitoring. Seven patients who received long-term (> 1 year) nocturnal nasal bilevel pressure ventilation with an expiratory pressure of <or= 4 cm H(2)O. Symptoms, pulmonary function, and arterial blood gas levels were assessed at each of three daytime sessions after the sequential 2-week periods using the different valves. Nocturnal studies used a multichannel recorder that measured heart rate, chest wall impedance, nasal airflow, and oximetry. End-tidal PCO(2) (PetCO(2)) from the mask and transcutaneous PCO(2) (PtcCO(2)) were also monitored nocturnally. Seven patients with a variety of neuromuscular, chest wall, and obstructive defects were enrolled. No mean differences in daytime arterial blood gas levels, pulmonary functions, nocturnal vital signs or oximetry, or PtcCO(2) were apparent regardless of the exhalation valve used. The multichannel recording was indicative of an air leak at least one third of the time, and the PetCO(2) tracing detected a blunted signal or no signal from the mask during the majority of the recording time. The use of an exhalation valve designed to minimize rebreathing did not improve daytime or nocturnal gas exchange or symptoms in patients receiving long-term nasal bilevel pressure ventilation in comparison with a traditional exhalation valve, most likely because of air leakage and escape of CO(2) via other routes.

Postoperative Pulmonary Changes after Laparoscopic Cholecystectomy

Postoperative Pulmonary Changes after Laparoscopic Cholecystectomy

Short acting beta agonists for recurrent wheeze in children under 2 years of age.

Wheeze is a common symptom in infancy and is a common cause for both primary care consultations and hospital admission. Beta2-adrenoceptor agonists (b2-agonists) are the most frequently used as bronchodilator but their efficacy is questionable. To determine the effectiveness of b2-agonist for the treatment of infants with recurrent and persistent wheeze. Relevant trials were identified using the Cochrane Airways Group database (CENTRAL), Medline and Pubmed. The database search used the following terms: Wheeze or asthma and Infant or Child and Short acting beta-agonist or Salbutamol (variants), Albuterol, Terbutaline (variants), Orciprenaline, Fenoterol Randomised controlled trials comparing the effect of b2-agonist against placebo in children under 2 years of age who had had two or more previous episodes of wheeze, not related to another form of chronic lung disease. Eight studies met the criteria for inclusion in this meta-analysis. The studies investigated patients in three settings: at home (3 studies), in hospital (2 studies) and in the pulmonary function laboratory (3 studies). The main outcome measure was change in respiratory rate except for community based studies where symptom scores were used. The studies were markedly heterogeneous and between study comparisons were limited. Improvement in respiratory rate, symptom score and oxygen saturation were noted in one study in the emergency department following two salbutamol nebulisers but this had no impact on hospital admission. There was a reduction in bronchial reactivity following salbutamol. There was no significant benefit from taking regular inhaled salbutamol on symptom scores recorded at home. There is no clear benefit of using b2-agonists in the management of recurrent wheeze in the first two years of life although there is conflicting evidence. At present, further studies should only be performed if the patient group can be clearly defined and there is a suitable outcome parameter capable of measuring a response.

Spirometry in the Supine Position Improves the Detection of Diaphragmatic Weakness in Patients With Amyotrophic Lateral Sclerosis

To determine which respiratory function tests best predicted diaphragmatic strength in patients with amyotrophic lateral sclerosis. Patients referred for pulmonary evaluation were included (n = 25) if they underwent measurement of transdiaphragmatic pressure (Pdi) and one or more of the following on the same day: upright FVC, supine FVC, upright FEV(1), supine FEV(1), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and PaCO(2). Abdominal paradox and use of accessory muscles were also assessed. Bivariate analyses were performed using simple linear regression. Sensitivity and specificity of the potential predictors to detect an abnormal Pdi (< 70 cm H(2)O) were calculated. Pulmonary function laboratory of an academic medical center. Upright FVC, FEV(1), and MEP were all significantly correlated with Pdi, while MIP and PaCO(2) were not. Supine FVC was the most highly correlated predictor of Pdi (R(2) = 0.76). A cutoff of supine FVC that was < 75% predicted was 100% sensitive and specific for predicting an abnormally low Pdi. Accessory muscle use and abdominal paradox were both significantly associated with Pdi, and the presence of accessory muscle use had a sensitivity of 84% and a specificity of 100% for detecting a low Pdi. Our findings suggest that supine FVC is an excellent and simple test of diaphragmatic weakness.

Respiratory Muscle Evaluation of the Patient with Neuromuscular Disease

This review presents clinically relevant issues regarding the assessment of respiratory muscles in individuals with neuromuscular disorders, and discusses the advantages and disadvantages of methods generally available to the clinician. Vital capacity (VC) and total lung capacity (TLC) are routinely measured in pulmonary function laboratories and are typically reduced in the context of severe respiratory muscle weakness, but the sensitivity and specificity of these measures are limited. Better measures of respiratory muscle weakness are maximal static inspiratory and expiratory pressures (PI max and PE max). PI max is reduced even with mild or moderate degrees of inspiratory muscle weakness, but low values also may be related to submaximal effort. To circumvent this problem, pressures can be measured using simpler maneuvers such as a maximal sniff. Specific tests of diaphragm function such as measurements of maximal transdiaphragmatic pressure are invasive and not routinely available to the clinician. Recently, noninvasive methods that specifically assess diaphragm function, such as diaphragm ultrasound of the zone of apposition and magnetic or electrophrenic nerve stimulation, have shown promise as new techniques for clinical use.

Methacholine Challenge: Test-Shortening Procedures

Validation of test-shortening procedures for the 2-min tidal breathing methacholine challenge method. Retrospective chart review. Tertiary-care university clinical pulmonary function laboratory. One thousand subjects aged 10 to 85 years (mean +/- SD, 44.5 +/- 16.0 years), 44.5% male, referred for methacholine challenge. Two-minute tidal breathing methacholine challenge was performed, with both physician and technician access to published test-shortening procedures. There were 315 positive test results (provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)] < or = 8 mg/mL) and 685 negative test results. The subjects with positive test results were less likely to be male (39.1 vs 47.5%; p < 0.02) and had lower FEV(1) (91.8 +/- 14.9% predicted vs 97.2 +/- 13.9% predicted; p < 0.001). The average starting PC(20) was between 0.5 mg/mL and 1.0 mg/mL; the most common PC(20) was 1 mg/mL (67%). There were 431 skipped concentrations in 380 subjects. The mean number of methacholine inhalations was 3.7 +/- 1.1 (3.9 +/- 0.1 for negative test results vs 3.3 +/- 1.2 for positive test results; p < 0.001). Eighteen subjects had a > or = 20% FEV(1) fall on the first inhalation, and 11 subjects had a > or = 20% FEV(1) fall after a skipped concentration. In only one case (0.1%) an FEV(1) fall > or = 40% on the first concentration was reported, compared with no cases after a skipped concentration and seven cases with a > or = 40% FEV(1) fall after a routine doubling dose step-up. The 2-min tidal breathing methacholine test in clinical practice can be safely shortened to an average of less than four inhalations using starting concentrations based on FEV(1), asthma medication, and clinical features, and by occasionally omitting concentrations.

Occupational Inhalant Exposure and Respiratory Disorders among Never-Smokers Referred to a Hospital Pulmonary Function Laboratory

Multiple reports have described associations between occupational inhalant exposure and lung disease. Previous occupational lung disease investigations have studied populations consisting of both smokers and nonsmokers. Smoking complicates interpretation of toxicant exposure-response relationships. The objective of this study was to determine whether, among never-smokers, occupational exposure to gases, dusts, or fumes is associated with a history of respiratory disorders and pulmonary function test defined obstructive lung disease. We performed a retrospective analysis of 517 never-smoker patients who underwent pulmonary function testing in our clinical laboratory between 1986 and 1999. We calculated the relative risks of developing adverse respiratory health outcomes given a history of exposure to occupational inhalants. Compared with persons with a negative occupational exposure history, exposed persons had an increased risk of reporting a history of bronchitis [relative risk (RR), 1.59; 95% confidence interval (CI), 1.20-2.12], recurrent lung infections (RR, 2.09; 95% CI, 1.14-3.82), and bronchodilator use (RR, 1.61; 95% CI, 1.26-2.06). There was also a statistically significant association between a history of inhalant exposure and the finding of an obstructive ventilatory defect on pulmonary function testing (RR, 1.79; 95% CI, 1.12-2.85). A history of inhalant exposure was not associated with self-reported asthma (RR, 1.08; 95% CI, 0.83-1.41). The population attributable risk estimates for respiratory disorders due to inhalant exposure were: bronchitis, 23.6%; recurrent lung infection, 36.3%; bronchodilator use, 24.3%; and obstructive lung disease, 29.6%. Occupational inhalant exposure is a strong risk factor for lung disease in this population of never smokers. A significant burden of respiratory disease in this population may be attributable to occupational inhalant exposure.

Off‐line exhaled nitric oxide measurements in children

The concentration of exhaled nitric oxide (eNO) is a useful marker of asthmatic bronchial inflammation. eNO can now be measured away from the laboratory (off-line), even in children. Short exhalation maneuvers (8 sec) and small samples (1 L) of exhaled gas are probably sufficient in children, but more information is needed about the effect of different measurement conditions. As a preliminary step before conducting epidemiological studies in schoolchildren, we investigated the effects of expiratory flow, dead space, and expiratory time on eNO concentrations collected in 1-L mylar collection bags. We studied 101 cooperative subjects (62 males) aged 5–18 years (30 healthy volunteers, 51 asthmatics, and 20 children with various other respiratory diseases) in our pulmonary function laboratory. On-line and off-line eNO were compared in a single session, and analyzed with a Sievers NOA™ 280 nitric oxide analyzer. For both methods of collecting expired gas, subjects did a single exhalation without breath-holding against an expiratory pressure 10 cm H2O. We investigated the effects of expiratory flow, dead space, and exhalation time on eNO; we also compared on-line and off-line eNO measurements, and the repeatability of both techniques at a given flow rate. Expiratory flows of 58 mL/sec provided more reproducible data than lower flows (coefficient of repeatability 1.1 ppb for 58 mL/sec vs. 2.8 for 27 mL/sec vs. 5.7 for 18 mL/sec). eNO concentrations were about 25% higher in off-line than in on-line recordings if the initial 250 mL of exhaled gas were not eliminated, and 37% higher if exhalation lasted longer (16 sec vs. 8 sec). Eliminating 250 mL of dead space and shortening the filling time to 8 sec yielded off-line eNO values close to those on-line (geometric mean off-line eNO 14.4 ppb, 95% confidence interval: 12.2–17.0) vs. on-line eNO 13.8 ppb (95% confidence interval: 11.6–16.5). On-line and off-line results were highly correlated (r = 0.996, P = 0.000) and had similar coefficients of variation (on-line eNO 2.6%, off-line 2.8%). Neither agreement nor repeatability of eNO measurements were affected by disease status or baseline FEV1 (% predicted values). Once standardized, the off-line eNO technique using 1-L gas collection bags will provide results similar to those recorded on-line. Pediatr Pulmonol. 2001; 32:159–167. © 2001 Wiley-Liss, Inc.

Predictors of Oxygen Desaturation During Submaximal Exercise in 8,000 Patients

To determine predictors of oxygen desaturation during submaximal exercise in patients with various lung diseases. This retrospective case series used pulmonary function laboratory results from all patients referred to a major tertiary-care center. 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). 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. 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.