Analysis of expiratory pattern for monitoring bronchial obstruction in school-age children

This study was designed to assess the validity of the percent of volume expired at tidal peak flow (dV/V_t) as an indicator of bronchial obstruction in school-age children. We analyzed 126 dV/V_t ratios and compared them with spirometric and plethysmographic results measured in 24 healthy (14 males) and 60 asthmatic (41 males) children; 42 of them underwent measurements before and after bronchial challenge with histamine. The two groups differed in resistance, forced expiratory volume in 1 sec (FEV₁), and forced expiratory flows, as percents of predicted (FEV₁: 94.6 ± 2.4% in controls vs 86.7 ± 1.6% in asthmatics; P<0.001). They did not differ in peak expiratory flow (PEF), forced vital capacity, functional residual capacity, measured by body plethysmography, and in d/V_t. The dV/V_t was found to correlate with FEV₁ (r=0.58, P<0.001), PEF (r=0.57, P<0.001), and other lung function parameters. Forty-two of the asthmatic children performed a bronchoprovocation histamine test. The fall of dV/V_t after histamine was significantly correlated (r=0.61, P<0.001) with the variation in FEV₁ and other lung function parameters. We conclude that dV/V_t is a good indicator of bronchial obstruction, as useful in school-age children as in adults and infants, with no need for the subject's cooperation. Pediatr Pulmonol 1991; 10:6–10.     

Effect of posture on ventilation and breathing pattern during room air breathing at rest

We measured minute ventilation (V_E), tidal volume (V_T), mean inspiratory flow (V_T/T_I), and occlusion pressure (P_.1) in 10 resting subjects breathing room air, in sitting, supine, right and left lateral positions, and compared them with corresponding data on static lung compliance [Cst(l)], dynamic lung compliance [Cdyn(l)], and pulmonary flow resistance [R(l)]. Highest values for V_T, V_E, V_T/T_I, P_.1, and effective inspiratory impedance [P_.1/(V_T/T_i)] were observed in the supine posture. Values for P_.1 and P_.1/(V_T/T_I in lateral decubitus were intermediate to those obtained when seated and supine. While the increases in P_.1 and P_.1/(V_T/T_I) in recumbent postures were qualitatively similar to the decrease in Cdyn(l) and increase in R(l), there was no significant correlation between them, probably reflecting the complex relationship between P_.1/(V_T/T_I) and lung compliance and resistance, as the former, in addition to lung mechanics, also depends on the shape of the inspiratory driving pressure wave, the active inspiratory impedance, the mechanics of the chest wall, and the duration of inspiration. An erratum to this article is available at .     

Chronic Exertional Dyspnea and Respiratory Muscle Function in Patients with Chronic Obstructive Pulmonary Disease

The symptom of breathlessness is an important outcome measure in the management of patients with chronic obstructive pulmonary disease (COPD). Clinical ratings of dyspnea and routine lung function are weakly related to each other. However, in the clinical setting breathlessness in COPD is encountered under conditions of increased respiratory effort, impeded respiratory muscle action, or functional weakness. Thus, the present study was carried out to determine whether and to what extent clinical ratings of dyspnea and respiratory muscle dysfunction relate to each other. In 21 patients with COPD two methods were used to rate dyspnea: a modified Medical Research Council Scale (MRC) and the Baseline Dyspnea Index (BDI), which is a multidimensional instrument for measuring dyspnea based on three components: magnitude of task, magnitude of effort, and functional impairment. A baseline focal score was obtained as the sum of the three components. Measures were: pulmonary volumes; arterial blood gases; maximal voluntary ventilation (MVV); maximal inspiratory and expiratory pressures (MIP and MEP, respectively); and breathing patterns ventilation (V_E), tidal volume (V_T), and respiratory frequency (Rf). In 15 patients pleural pressure was also measured during both quiet breathing (Ppl_sw) and maximal inspiratory sniff maneuver at FRC (Pplsn). BDI and MRC ratings related to each other and showed comparable weak associations with standard parameters (FEV₁, Paco ₂, V _T), MIP, and MEP. In contrast, MVV closely and similarly related to both ratings. Ppl_sw (%Ppl_sn), a measure of respiratory effort, and Ppl_sw (%Ppl_sn)/V _T(%VC), an index of neuroventilatory dissociation, related significantly to both the BDI (r ²=−0.77 and r ²=−0.75, respectively) and the MRC (r ²= 0.81 and r ²= 0.74, respectively). Using MVV, Ppl_sw (%Ppl_sn), and Ppl_sw (%Ppl_sn)/V _T(%VC) in a stepwise multiple regression as independent variables with BDI rating as dependent variable, MVV explained an additional 14.5% of the variance of the BDI over the 67.8% predicted by Ppl_sw (%Ppl_sn). Our results demonstrate that the level of chronic exertional dyspnea in COPD increases as the ventilatory muscle derangement increases. The level of the relationships among dyspnea ratings and MVV and respiratory effort helps to explain some of the mechanisms of chronic dyspnea of COPD. These measures should be considered for therapeutic intervention to reduce dyspnea. Accepted for publication: 30 December 1996     

Assessment of Breathlessness Perception by Borg Scale in Asthmatic Patients: Reproducibility and Applicability to Different Stimuli

In asthmatics, the score of bronchoconstriction-associated breathlessness at 20% fall in forced expiratory volume at first second (FEV₁) evaluated on a Borg scale (PS₂₀) is a tool successfully used to measure the perception of symptoms. This prospective laboratory study evaluated the applicability of PS₂₀ to assess the breathlessness induced by ultrasonically nebulized distilled water (UNDW) and methacholine (M) and its reproducibility. Twenty-two mild and clinically stable asthmatic patients performed UNDW and M challenge tests. The PS₂₀ was calculated by linear interpolation of the last two points of the perception/fall in FEV₁ curve of the UNDW and M tests. The reproducibility of PS₂₀ M was assessed by repeating measurements on 2 separate days by 3 weeks. PS₂₀ UNDW and PS₂₀ M did not differ and were respectively 1.82 ± 1.85 and 2.03 ± 1.86. They were significantly related (r_s = 0.63; p<0.01) and the bias between PS₂₀ UNDW and PS₂₀ M was –0.21 with the limits of agreement ranging from –3.2 to 3.6. The intraclass correlation coefficient for repeated measurement of PS₂₀ M was 0.82; the bias between the two measurements was 0.2 with the limits of agreement ranging from –2.8 to 3.2. All patients had a measurable breathlessness perception degree on a Borg scale during both distilled water challenges and methacholine. Asthmatic patients with normal, exaggerated or poor breathlessness perception were also similar for both stimuli. In addition, PS₂₀ showed a good reproducibility and this allows the serial evaluation of patient's breathlessness perception by this technique in clinical settings and in the physiology laboratory.     

Are tidal breathing indices useful in infant bronchial challenge tests?

Tidal breathing indices have been used to assess histamine-induced airway obstruction in adults and children. The aim of this study was to see whether they could be used to assess histamine challenge in infants. Tidal flow during quiet breathing was measured using a face mask and pneumotachograph and maximum flow at functional residual capacity (V_maxFRC) was measured from partial forced expirations in 18 sleeping, sedated infants who responded to histamine challenge and in 18 nonresponders. The tidal indices calculated were inspiratory and expiratory time (t₁, and t_e), tidal peak expiratory flow (PEF), mean tidal expiratory flow rate (V_T/t_e) and the expiratory time constant of the respiratory system (t_rs). The time to maximal expiration divided by expiratory time (t_me/t_e) and 2 revised forms of this index (t_me(a)t_e and t_me(b)( t_me(b) /t_e) were also calculated. Recordings of t_me(a) and t_me(b) were taken at 95% of peak tidal expiratory flow, before and after the peak, respectively. In nonresponders, there was an insignificant mean rise in V_maxFRC of 11.8% but no change in any tidal index. In responders, the mean percentage fall in V_maxFRC was 43.3% (range, ?31 to ?81%); t_rs fell from 0.61 s to 0.51 s (P < 0.05) and breathing frequency and mean tidal expiratory flow rate increased from 34.0 to 37.5 min^?1 (P < 0.01) and from 66.6 to 72.6 mL.s^?1 (P < 0.05), respectively, suggesting that infants had adopted a strategy of active expiration in response to bronchial challenge. There was no change either in t_me/t_e, or in the revised indices after challenge., It is therefore concluded that t_me/t_e is an insensitive index of airflow obstruction compared to V_maxFRC and cannot be used to assess the response to bronchial challenge. Changes in other indices were small and related to a presumed pattern of active expiration after challenge. Pediatr Pulmonol. 1994; 17:225–230. © 1994 Wiley-Liss, Inc.     

A step in the right direction: Assessing exercise tolerance in cystic fibrosis

Exercise tolerance may be reduced in patients with cystic fibrosis, but it is not always possible to predict this from standard lung function measurements. Formal exercise testing may, therefore, be necessary, and the test should be simple and readily available. We have developed a “3-minute step test” and compared it with the standard 6-minute walking test. Subjects stepped up and down a 15-cm-high single step at a rate of 30 steps per minute for 3 minutes. The effect of the step test on spirometry was tested first in 31 children with CF (mean age, 12.0 years), who had a mean (range) baseline forced expired volume in 1 second (FEV₁) of 64% (18–94%) of predicted values. The step test was then compared with the standard 6-minute walk in a further 54 patients with cystic fibrosis (mean age, 12.5 years), with mean (range) baseline FEV₁ of 61% (14–103%) of predicted values. Outcome measures were minimum arterial oxygen saturation (SaO₂), maximum pulse rate, and the modified Borg dyspnea score. Post-step test spirometry showed mean (95% CI) changes of −1.1% (−6.0+3.9%) for forced vital capacity, of −1.6% (−4.2+1.1%) for FEV₁, and +0.25% (−2.8+3.3%) for peak expiratory flow, although 5/31 children showed >15% drop in one or more parameters. The step and walk tests both produced significant changes (P < 0.0001) in all outcomes, with a mean (range) minimum SaO₂ of 92% (75–98%) versus 92% (75–97%), a maximum pulse rate of 145 b.p.m. (116–189) versus 132 (100–161), and a Borg score of 2.5 (0–9) versus 1.0 (0–5), respectively. Comparison of the two tests showed that the step test increased breathlessness (mean change Borg score, 2.3 vs. 0.8; P < 0.0001) and pulse rate (mean change, 38% vs. 24%, P < 0.0001) significantly more than the walk, whereas the decrease in SaO₂ was similar (mean change, −2.9% vs. −2.6%; P = 0.12). Some patients with a significant drop in SaO₂ (>4%) would not have the decrease predicted from their baseline lung function. Reproducibility for the two tests was similar. The step test is quick, simple and portable, and is not dependent on patient motivation. Although the step test is more tiring, its effect on SaO₂ is similar to the 6-minute walking test. It is a safe test that may prove to be a valuable measure of exercise tolerance in children with pulmonary disease, although longitudinal studies are now needed. Pediatr Pulmonol. 1998; 25:278–284. © 1998 Wiley-Liss, Inc.     

Intercept of minute ventilation versus carbon dioxide output relationship as an index of ventilatory inefficiency in chronic obstructive pulmonary disease

BackgroundVentilatory inefficiency contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). The intercept of the minute ventilation (V^˙ _E) vs. carbon dioxide output (V^˙ CO₂) plot is a key ventilatory inefficiency parameter. However, its relationships with lung hyperinflation (LH) and airflow limitation are not known. This study aimed to evaluate correlations between the V^˙ _E/V^˙ CO₂ intercept and LH and airflow limitation to determine its physiological interpretation as an index of functional impairment in COPD.MethodsWe conducted a retrospective analysis of data from 53 COPD patients and 14 healthy controls who performed incremental cardiopulmonary exercise tests (CPETs) and resting pulmonary function assessment. Ventilatory inefficiency was represented by parameters reflecting the V^˙ _E/V^˙ CO₂ nadir and slope (linear region) and the intercept of V^˙ _E/V^˙ CO₂ plot. Their correlations with measures of LH and airflow limitation were evaluated.ResultsCompared to control, the slope (30.58±3.62, P<0.001) and intercept (4.85±1.11 L/min, P<0.05) were higher in COPD_stages1-2, leading to a higher nadir (31.47±4.47, P<0.01). Despite an even higher intercept in COPD_stages3-4 (7.16±1.41, P<0.001), the slope diminished with disease progression (from 30.58±3.62 in COPD_stages1-2 to 26.84±4.96 in COPD_stages3-4, P<0.01). There was no difference in nadir among COPD groups and higher intercepts across all stages. The intercept was correlated with peak V^˙ _E/maximal voluntary ventilation (MVV) (r=0.489, P<0.001) and peak V^˙ O₂/Watt (r=0.354, P=0.003). The intercept was positively correlated with residual volume (RV) % predicted (r=0.571, P<0.001), RV/total lung capacity (TLC) (r=0.588, P<0.001), peak tidal volume (V_T)/FEV₁ (r=0.482, P<0.001) and negatively correlated with rest inspiratory capacity (IC)/TLC (r=−0.574, P<0.001), peak V_T/TLC (r=−0.585, P<0.001), airflow limitation forced expiratory volume in 1 s (FEV₁) % predicted (r=−0.606, P<0.001), and FEV₁/forced vital capacity (FVC) (r=−0.629, P<0.001).ConclusionsV^˙ _E/V^˙ CO₂ intercept was consistently correlated with worsening static and dynamic LH, pulmonary gas exchange, and airflow limitation in COPD. The V^˙ _E/V^˙ CO₂ intercept emerged as a useful index of ventilatory inefficiency in COPD patients.     

Effect of α-tocopherol on lipid peroxidation and total antioxidant status in spontaneously hypertensive rats

The aim of this study was to determine the effects of α-tocopherol on lipid peroxidation and total antioxidant status of spontaneously hypertensive rats (SHR), comparing them with normal Wistar-Kyoto (WKY) rats. SHR were divided into three groups and treated with different doses of α-tocopherol (α₁, 17 mg/kg diet; α₂, 34 mg/kg diet; and α₃, 170 mg/kg diet). Normal WKY and untreated SHR were used as normal (N) and hypertensive control (HC). Blood pressures were recorded every 10 days for 3 months. At the end of the trial, animals were killed and measurement of plasma total antioxidant status, plasma superoxide dismutase (SOD) activity, and lipid peroxide levels in plasma and blood vessels was carried out following well-established methods.From our study it was found that lipid peroxides in thoracic aorta (N, 0.47 ± 0.17; H, 0.96 ± 0.37; P < .0001) and plasma (N, 0.06 ± 0.01; H, 0.13 ± 0.01) were significantly higher in hypertensives than in normal rats. SOD activity was significantly lower in hypertensive than normal rats (N, 172.93 ± 46.91; H, 110.08 ± 14.38; P < .005). Total antioxidant status was significantly higher in normal than hypertensive rats (N, 0.88 ± 0.05; H, 0.83 ± 0.02; P < .05). After the antioxidant trial, it was found that in the treated groups rise of blood pressure was prevented significantly (P < .001) and lipid peroxides in blood vessels were significantly reduced more than in the controls (P < .001). For plasma lipid peroxide it was only significant for groups α₂ (P < .001) and α₃ (P < .05). Although all three treated groups showed improved total antioxidant status, only groups α₂ (0.87 ± 0.04, P < .005) and α₃ (1.20 ± 0.18, P < .001) were statistically significant. All the three groups showed significant increases in their SOD activity (P < .001).Correlation studies showed that total antioxidant status and SOD were significantly negatively correlated with blood pressure in normal rats (P = .007; P = .008). Lipid peroxides in both blood vessel and plasma showed a positive correlation. In the treated groups, lipid peroxides in blood vessels maintained a significant positive correlation with blood pressure in all groups (α₁, P = .021; α₂, P = .019; α₃, P = .002), whereas for plasma lipid peroxides the correlation was in groups α₁ (P = .005) and α₂ (P = .009). For SOD activity, significant negative correlations were found with blood pressure in the α₂ (P = .017) and α₃ (P = .025) groups. Total antioxidant status maintained a significant negative correlation with blood pressure in all three groups (α₁, P = .012; α₂, P = .044; α₃, P = .014).In conclusion it was found that supplement of α-tocopherol may prevent development of increased blood pressure, reduce lipid peroxides in plasma and blood vessels, and enhance the total antioxidant status, including SOD activity.     

Breathing Pattern and Ventilatory Control in Chronic Tetraplegia

Blunted ventilatory responses to carbon dioxide indicate that respiratory control is impaired when ventilation is stimulated in individuals with tetraplegia; however, respiratory control during resting breathing has not been extensively studied in this population. Our objective was to evaluate respiratory control and sigh frequency during resting breathing in persons with tetraplegia. A prospective, two-group comparative study was performed. Breathing pattern was assessed in ten outpatients with chronic tetraplegia and eight age- and gender-matched able-bodied controls. Subjects were noninvasively monitored for 1 h, while seated and at rest. Tidal volume (V_T) was calculated from the sum of the anteroposterior displacements of the rib cage and abdomen and the axial displacement of the chest wall. Inspiratory time (T_I), V_T, and the ratio of V_T to inspiratory time (V_T/T_I) were calculated breath by breath. A sigh was defined as any breath greater than two or more times an individual’s mean V_T. Minute ventilation, V_T/T_I, and sigh frequency were reduced in tetraplegia compared with controls (5.24 ± 1.15 vs. 7.16 ± 1.29 L/min, P < 0.005; 208 ± 45 vs. 284 ± 47 ml/s, P < 0.005; and 11 ± 7 vs. 42 ± 19 sighs/h, P < 0.0005, respectively). V_T/T_I was associated with sigh frequency in both groups (tetraplegia: R = 0.88; P = 0.001 and control: R = 0.70; P < 0.05). We concluded that reductions in minute ventilation, V_T/T_I, and sigh frequency suggest that respiratory drive is diminished during resting breathing in subjects with tetraplegia. These findings extend prior observations of disordered respiratory control during breathing stimulated by CO₂ in tetraplegia to resting breathing.     

Determinants of the tension-time index of inspiratory muscles in children with cystic fibrosis

Nutritional status and chronic pulmonary hyperinflation can alter respiratory muscle function in cystic fibrosis (CF). This study investigated: 1) whether inspiratory muscle function is reduced in children with stable CF in comparison with healthy controls; and 2) the mechanisms leading to inspiratory muscle weakness, which probably predispose to respiratory muscle fatigue. We determined the tension-time index of the inspiratory muscles (T_TMUS) noninvasively at rest in 16 children with mild to moderate CF (mean age, 11 ± 2 years) and 10 healthy controls (mean age, 11 ± 2 years). The T_TMUS was determined as follows: T_TMUS = T_I/T_TOT · P_I/P_IMAX, where P_I is the mean inspiratory pressure estimated from the measure of mouth occlusion pressure (P0.1), P_IMAX is the maximal inspiratory pressure, and T_I/T_TOT is the duty cycle. The results showed similar nutritional status in both groups, as well as mild to moderate airway obstruction, hyperinflation, and trapped gas in the CF group. In this group only, a significant inverse relationship was found between T₁/T_TOT and P₁/P_IMAX[T_IT_TOT = 0.482 - (0.388P_I/P_IMAX), r = −0.53; p < 0.05]. The patients also had a greater T_TMUS (T_TMUS = 0.087 ± 0.030 in CF vs. 0.056 ± 0.014 in controls, P < 0.01) that increased with decreasing lean body mass (r = −0.70, P < 0.005), with increasing percent predicted functional residual capacity (r = 0.70, P < 0.05). and increasing volumes of trapped gas (r = 0.77, P < 0.01). The multiple linear regression analysis for these factors was significant (R² = 0.84, P < 0.01); however, the partial regression coefficient was significant only for lean body mass (r² = 0.60, P < 0.05). Therefore, muscle mass appeared as the strongest determinant of T_TMUS in CF. This study used a noninvasive method to assess the inspiratory muscle performance in children with CF. The results suggest impairment in inspiratory muscle function in these children despite good nutritional status and only mild to moderate alteration in pulmonary function tests. In addition, we were able to investigate some of the determinants of inspiratory muscle weakness, namely, muscle mass, hyperinflation, and trapped gas, and found that muscle mass played a predominant role. Pediatr. Pulmonol. 1997; 23:336–343. © 1997 Wiley-Liss, Inc.     

Assessment of forced expiratory volume — time parameters in detecting histamine-induced bronchoconstriction in wheezy infants

A new technique recently introduced allows the measurement of infant lung function from lung volumes raised by a pump prior to generation of forced expiratory flow-volume (FEFV) curves. Forced expiratory volume-time (FEV₁) parameters rather than traditional flow parameters are used. The aim of this study was to assess the usefulness of FEV, parameters in detecting airway responsiveness to histamine in recurrently wheezy infants. Ten infants (age 7–18 months) sedated with 80 mg/kg chloral hydrate underwent a histamine inhalation challenge. Throughout the challenge FEFV curves were generated from end-tidal inspiration. Raised FEFV curves, from a lung volume preset by 15 cmH₂O inflation pressure, were gathered at baseline and after the final concentration of histamine. The mean fall from baseline was 47% in maximal flow at functional residual capacity (VmaxFRC) (P < 0.0005), 15.5% in FEV_0.5 (P < 0.000l), 13.5% in FEV_0.75 (P < 0.005), and 11.0% in FEV_1.0 (P = 0.057), after the final concentration of histamine delivered. Tidal volume and inspiratory volume reached above FRC between pre- and posthista-mine did not change. Mean oxygen saturation fell significantly from 97 to 93%. We conclude that FEV₁ parameters adequately detect reduced lung function during histamine-induced bronchoconstriction and appear suitable for histamine challenge testing in infants. © 1993 Wiley-Liss, Inc.     

The prevalence and predictors of airway hyperresponsiveness in sarcoidosis

Background and objective: Obstructive airflow limitation is the most common physiological impairment in sarcoidosis. This study determined the prevalence of airway hyperresponsiveness (AHR) in sarcoidosis, the correlation between responses to direct (using histamine) and indirect (using hypertonic saline) bronchial challenge, and the clinical, physiological and radiological predictors of AHR. Methods: Subjects with sarcoidosis and a baseline forced expiratory volume in 1 s (FEV₁) >35% predicted underwent hypertonic and histamine challenge, lung function testing and high resolution computed tomography (HRCT) of the chest. AHR was defined as a 15% fall in FEV₁ to hypertonic saline and a 20% fall in FEV₁ to histamine. Results: The 52 subjects had well‐preserved lung function (FEV₁ = 2.8 ± 0.7 L, 87% predicted). AHR was detected in 5/47 (11%) to hypertonic saline and 19/43 (44%) to histamine challenge. On univariate analysis, response to histamine challenge was predicted by conglomerate fibrosis (P = 0.02) and reticular pattern (P = 0.03) on HRCT. The baseline % predicted forced expiratory volume in 1 s was significantly inversely associated with AHR on univariate (P = 0.004) and multivariate analysis (P = 0.01) when adjusted by HRCT patterns. Conclusions: The higher prevalence of AHR using histamine challenge than hypertonic saline challenge and the association with baseline % predicted FEV₁ suggest that the AHR in sarcoidosis may reflect the consequences of airway remodelling following inflammation.     

Bi-level Positive Airway Pressure (BiPAP) with Standard Exhalation Valve Does Not Improve Maximum Exercise Capacity in Patients with COPD

Background: Although BiPAP has been used as an adjunct to exercise, little is know about its effect on exercise in COPD. We aimed to evaluate the acute effect of BiPAP delivered with a standard valve (Vision, Respironics), compared to no assist, on exercise capacity in individuals with COPD. Methods: Peak exercise workload (WL_peak), dyspnea (Borg), end-expiratory lung volume (EELV), tidal volume (V_T), minute ventilation (V_E), O₂ uptake (VO₂), and CO₂ production (VCO₂) were assessed in 10 COPD patients (FEV₁ 53 ± 22% pred) during three symptom-limited bicycle exercise tests while breathing i) without a ventilator (noPS), ii) with a pressure support (PS) of 0 cm H₂O (PS0; IPAP & EPAP 4 cm H₂O) and iii) PS of 10 cm H₂O (PS10; IPAP 14 & EPAP 4 cm H₂O) on separate days using a randomized crossover design. Results: WL_peak was significantly lower with PS10 (33 ± 16) and PS0 (30.5 ± 13) than noPS (43 ± 19) (p < 0.001). Dyspnea at peak exercise was similar with noPS, PS0 and PS10; at isoload it was lower with noPS compared to PS10 and PS0 (p < 0.01). V_T and V_E were highest with PS10 and lowest with noPS both at peak exercise and isoload (p < 0.001). EELV was similar at peak exercise with all three conditions. VO₂ and VCO₂ were greater with PS10 and PS0 than noPS (p < 0.001), both at peak exercise and isoload. Conclusion: Use of BiPAP with a standard exhalation valve during exercise increases V_T and V_E at the expense of augmenting VCO₂ and dyspnea, which in turns reduces WL_peak in COPD patients.     

Two-month comparative study of tulobuterol aerosol versus fenoterol aerosol in patients with chronic obstructive lung disease

In this two month, double-blind, crossover study, the efficacy and safety of tulobuterol aerosol (400μg qid) was compared to fenoterol aerosol (400μg qid) in patients with chronic obstructive lung disease. Thirty-six (36) adults with reversible bronchospasm were enrolled. All patients were evaluable. On set of response was within 5 minutes for both drugs. Mean increases in FEV₁ were greater after tulobuterol than fenoterol at every time interval. Increases peaked at 30–60 minutes postdose. Duration of response was longer after tulobuterol with mean FEV₁ remaining >15% over baseline for at least 6 hours postdose. Mean predose FEV₁ values were significantly greater after 2 and 4 weeks of tulobuterol treatment compared with fenoterol. Despite these large increases, changes in mean FEV₁ from predose to 1 hour postdose at these visits were not significantly different between treatment groups. Results of plethysmography testing also indicated greater improvement after tulobuterol. In addition, improvement in pulmonary symptoms was more pronounced during tulobuterol therapy. Small changes in mean blood pressure occurred, with greater changes after fenoterol than after tulobuterol. Changes in mean pulse rate were significantly greater following fenoterol administration. No adverse reactions were reported during tulobuterol treatment; however, one patient experienced severe tremor, tachycardia, and sweating during fenoterol treatment and withdrew from the study prematurely. The results in this study indicate that tulobuterol aerosol is more effective than fenoterol aerosol in the treatment of patients with chronic obstructive lung disease, with fewer cardiovascular effects and no adverse reactions.     

Frequency distribution of breath sounds as an indicator of bronchoconstriction during histamine challenge test in asthmatic children

In order to study changes in respiratory sounds associated with acute bronchoconstriction and -dilatation, breath sounds of 11 children with asthma (age range, 10–14 years) were recorded at the chest and at the trachea during histamine challenge test and after subsequent bronchodilatation. The changes in frequency spectra of breath sounds were compared with simultaneous changes in forced expiratory volume in 1 second (FEV₁). In seven children who responded to histamine with a decrease in FEV, of more than 15%, there was a significant relationship between percentage change in FEV₁ (ΔFEV₁) and percentage change in median frequency (ΔF50) of expiratory breath sounds recorded at the chest (r = 0.865; β = ?0.706, P = 0.0001) and at the trachea (r = 0.888; β = 1.12, P = 0.0001). The association between breath sound intensity and FEV₁ was weaker. Based on ANOVA, the increase of F50 during the challenge test was significantly larger in children who responded to histamine than in those who were non-responsive (P = 0.0016). At the chest, a decrease of 15% in FEV₁ corresponded to an increase of 8% in expiratory F50. The provocative dose of histamine inducing a decrease of 15% in FEV₁ (PD15FEV₁) and the provocative dose causing an increase of 8% in F50 (PD8F50) were significantly related (r = 0.927, P = 0.003). We conclude that spectral analysis of breath sounds can be used to indicate airway obstruction during bronchial challenge tests in children, and may be adapted for tests in pre-school children. The results suggest that the same mechanisms that induce airflow limitation due to inhaled histamine may generate an increase in frequency content of breath sounds in children with asthma. Pediatr Pulmonol. 1994;18:170–177. © 1994 Wiley-Liss, Inc.     

Changes in lung mechanics following sighs in premature newborns without lung disease

Sighs, the interspersed breaths of larger tidal volume (V_T) than those preceding or following them, occur more frequently in the newborn than in adults. It has been postulated that the sigh augments functional residual volume (FRC), increases lung compliance (CJ, and recruits atelectatic alveoli. Since the premature infant has relatively low FRC, we hypothesized that sighs might be more frequent in these babies and that C_L could be shown to change before and/or after a sigh. We studied 14 premature infants (gestational age, 30 ± 2.2 weeks; mean ± SD) without lung disease during quiet sleep. Minute ventilation (V_E) was measured by pneumotachography and pleural pressure changes via a water-filled catheter in the esophagus. In the 78 sighs examined, the incidence was 0.71 sighs/min, similar, to previous reports for full-term newborns. There was no change in respiratory frequency, V_T/V_E, nor mean inspiratory flow (V_T/T_t, where T_t is the inspiratory time) before or after the event. The volume of the sigh increased from 7.8 ± 0.2 mL/kg to 21.5 ± 0.5 mL/kg, in concert with an increase in breath duration (T_TOT) from 0.98 ± 0.02 ± to 2.56 ± 0.12 s, resulting in an unchanged V_E, V_T/T_I). and respiratory duty cycle (T_I/T_TOT/). This suggests that the increased V_T was matched by a prolongation in both T_I and T_TOT. Following the sigh, C_L increased from 1.43 ± 0.13 cmH₂O/kg to 1.66 ± 0.27 cmH₂O/L/s/kg (paired t-test, P < 0.001) whilst the lung resistance R_L, fell from 62 ± 8 cmH₂O/L/s/kg to 55 ± 3.8 cmH₂O/L/s/kg (P < 0.05). As reflected by the end—expiratory volume (EEV), FRC did not change. This stability of FRC, coupled with the increase in C_L and fall in R_L, suggests a recruitment of atelectatic acini with a redistribution of lung volume, such that the previously atelectatic and overdistended acini achieve a more optimal pressureivolume relationship following a sigh. Pediatr Pulmonol. 1994; 17:22–25. © 1994 Wiley-Liss, Inc.     

Reduction of increased levels of blood glycerol and ketone bodies by propranolol in human hyperthyroidism: Role of the fall of the triiodothyronine level

Hyperthyroid patients in the postabsorptive state have elevated levels of blood glycerol and ketone bodies (KB): this is believed to be due to increased lipolysis and ketogenesis. These increased glycerol and KB levels return toward normal after oral propranolol administration. In order to investigate the mechanism of action of propranolol in hyperthyroid patients, we compared the effects of the oral administration of propranolol with those of timolol, propylthiouracil (PTU), and a placebo. The placebo had no effect. The free thyroxine index, immunoreactive insulin level and glucagon level were not modified by propranolol, timolol, or PTU. Propranolol decreased the pulse rate (P < 0.01) and the levels of serum triiodothyronine (T₃; P < 0.05), blood glycerol (P < 0.01), and KB (P < 0.01). Like propanolol, timolol decreased the pulse rate (P < 0.01) but had no effect on the T₃, glycerol, or KB levels. Propylthiouracil did not modify the pulse rate, but like propanolol, it decreased the T₃ (P < 0.05), glycerol (P < 0.01) and KB (P < 0.01) levels. These results suggest that the metabolic actions of propranolol are not caused by its hemodynamic effects nor its beta-blocking properties but are mediated by the decrease of the T₃ level.     

Immediate response to inspiratory resistive loading in anesthetized patients with kyphoscoliosis: Spirometric and neural effects

In kyphoscoliosis (KS), lung volumes are reduced, respiratory elastance and resistance are increased, and breathing pattern is rapid and shallow, attributes that may contribute to defense of tidal volume (V_T) in the face of inspiratory resistive loading. The control of ventilation of 12 anesthetized patients about to undergo corrective spinal surgery was compared to that of 11 anesthetized patients free of cardiothoracic disease during quiet breathing and the first breath through one of three linear resistors. Mean forced vital capacity (FVC) of the KS group was 48% that of the controls (C). Passive elastance (Ers) and active elastance and resistance (Ers and Rrs, respectively) were computed according to previously described techniques (Behrakis PK, Higgs BD, Baydur A, Zin WA, Milic-Emili J (1983) Active inspiratory impedance in halothane-anesthetized humans. J Appl Physiol 54:1477–1481). Baseline tidal volume V_T, inspiratory duration T_I, expiratory duration T_E, duration of total breathing cycle T_T, and inspiratory duty cycle T_I/T_T were significantly reduced, while V_E was slightly decreased in the KS. Ers, Ers, and Rrs, were, respectively, 72, 69, and 89% greater in the KS. Driving pressure (Pmus) was derived from the equation of motion, using active values of respiratory elastance. With resistive loading, there was greater prolongation of T_I in the C, while percent reduction in V_T and minute ventilation V_E was less in KS. Compensation in both groups was achieved through three changes in the Pmus waveform. (1) Peak amplitude increased. (2) The duration of the rising phase increased. (3) The rising Pmus curve became more concave to the time axis. These changes were most marked with application of the highest resistance in both groups. Peak driving pressure and mean rate of rise of Pmus were greater in the KS. Increased intrinsic impedance, Pmus, and differences in changes in neural timing in anesthetized kyphoscoliotics contribute to modestly greater VT defense, compared to that of anesthetized subjects free of cardiorespiratory disease. Offprint requests to: Ahmet Baydur     

Comparison of supine and prone noninvasive measurements of breathing patterns in fullterm newborns

The current study was undertaken to ascertain whether shift from supine to prone posture alters the pattern of natural breathing in healthy fullterm newborns. Breathing patterns were measured in the supine and prone posture in 20 healthy fullterm infants using calibrated, noninvasive respiratory inductive plethysmography (RIP). The values for breathing pattern components in supine and prone postures expressed as means (± SD) were, respectively, tidal volume (V_T), 14.1(± 3.2) and 18.9(± 4.9)mL; mean inspiratory flow 26.7(± 11.5) and 32.8(± 13.0)mL/s; and minute ventilation 232(± 75) and 288(± 96)mL/kg/min (P < 0.01). Less thoracoabdominal incoordination, expressed as the labored breathing index (LBI), occurred with shift from supine to prone posture in infants studied in the active behavioral stage, changing from 2.0(± 0.5) to 1.3(± 0.4) (P < 0.01). Placement of a facemask-pneumotachograph system increased V, measured with RIP by 26% in the supine, and 18% in the prone posture. Neither respiratory rate nor inspiratory time (T_i) changed with the postural shift. Therefore, change from supine to prone posture improved ventilation and increased respiratory drive as expressed by V_T/T_i. Further, thoracoabdominal incoordination which took place during active sleep in the supine posture, lessened with change to the prone posture. Pediatr Pulmonol. 1994; 18:8–12. © 1994 Wiley-Liss. Inc.