Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study.

BACKGROUND: Small airways dysfunction (SAD) is well recognised in asthma, yet its role in the severity and control of asthma is unclear. This study aimed to assess which combination of biomarkers, physiological tests, and imaging markers best measure the presence and extent of SAD in patients with asthma. METHODS: In this baseline assessment of a multinational prospective cohort study (the Assessment of Small Airways Involvement in Asthma [ATLANTIS] study), we recruited participants with and without asthma (defined as Global Initiative for Asthma severity stages 1-5) from general practices, the databases of chest physicians, and advertisements at 29 centres across nine countries (Brazil, China, Germany, Italy, Spain, the Netherlands, the UK, the USA, and Canada). All participants were aged 18-65 years, and participants with asthma had received a clinical diagnosis of asthma more than 6 months ago that had been confirmed by a chest physician. This diagnosis required support by objective evidence at baseline or during the past 5 years, which could be: positive airway hyperresponsiveness to methacholine, positive reversibility (a change in FEV1 ≥12% and ≥200 mL within 30 min) after treatment with 400 µg of salbutamol in a metered-dose inhaler with or without a spacer, variability in peak expiratory flow of more than 20% (measured over 7 days), or documented reversibility after a cycle (eg, 4 weeks) of maintenance anti-asthma treatment. The inclusion criteria also required that patients had stable asthma on any previous regular asthma treatment (including so-called rescue ß2-agonists alone) at a stable dose for more than 8 weeks before baseline and had smoked for a maximum of 10 pack-years in their lifetime. Control group participants were recruited by advertisements; these participants were aged 18-65 years, had no respiratory symptoms compatible with asthma or chronic obstructive pulmonary disease, normal spirometry, and normal airways responsiveness, and had smoked for a maximum of 10 pack-years. We assessed all participants with spirometry, body plethysmography, impulse oscillometry, multiple breath nitrogen washout, CT (in selected participants), and questionnaires about asthma control, asthma-related quality of life (both in participants with asthma only), and health status. We applied structural equation modelling in participants with asthma to assess the contribution of all physiological and CT variables to SAD, from which we defined clinical SAD and CT SAD scores. We then classified patients with asthma into SAD groups with model-based clustering, and we compared asthma severity, control, and health-care use during the past year by SAD score and by SAD group. This trial is registered with ClinicalTrials.gov, number NCT02123667. FINDINGS: Between June 30, 2014, and March 3, 2017, we recruited and evaluated 773 participants with asthma and 99 control participants. All physiological measures contributed to the clinical SAD model with the structural equation modelling analysis. The prevalence of SAD in asthma was dependent on the measure used; we found the lowest prevalence of SAD associated with acinar airway ventilation heterogeneity (Sacin), an outcome determined by multiple breath nitrogen washout that reflects ventilation heterogeneity in the most peripheral, pre-acinar or acinar airways. Impulse oscillometry and spirometry results, which were used to assess dysfunction of small-sized to mid-sized airways, contributed most to the clinical SAD score and differed between the two SAD groups. Participants in clinical SAD group 1 (n=452) had milder SAD than group 2 and comparable multiple breath nitrogen washout Sacin to control participants. Participants in clinical SAD group 2 (n=312) had abnormal physiological SAD results relative to group 1, particularly their impulse oscillometry and spirometry measurements, and group 2 participants also had more severe asthma (with regard to asthma control, treatments, exacerbations, and quality of life) than group 1. Clinical SAD scores were higher (indicating more severe SAD) in group 2 than group 1, and we found that these scores were related to asthma control, severity, and exacerbations. We found no correlation between clinical SAD and CT SAD scores. INTERPRETATION: SAD is a complex and silent signature of asthma that is likely to be directly or indirectly captured by combinations of physiological tests, such as spirometry, body plethysmography, impulse oscillometry, and multiple breath nitrogen washout. SAD is present across patients with all severities of asthma, but it is particularly prevalent in severe disease. The clinical classification of SAD into two groups (a milder and a more severe group) by use of impulse oscillometry and spirometry, which are easy to use, is meaningful given its association with GINA severity stages, asthma control, quality of life, and exacerbations. FUNDING: Chiesi Farmaceutici SpA.

Application of long-period-grating sensors to respiratory plethysmography.

A series of in-line curvature sensors on a garment are used to monitor the thoracic and abdominal movements of a human during respiration. These results are used to obtain volumetric tidal changes of the human torso in agreement with a spirometer used simultaneously at the mouth. The curvature sensors are based on long-period gratings (LPGs) written in a progressive three-layered fiber to render the LPGs insensitive to the refractive index external to the fiber. A curvature sensor consists of the fiber long-period grating laid on a carbon fiber ribbon, which is then encapsulated in a low-temperature curing silicone rubber. The sensors have a spectral sensitivity to curvature, d lambda/dR from approximately 7-nm m to approximately 9-nm m. The interrogation technique is borrowed from derivative spectroscopy and monitors the changes in the transmission spectral profile of the LPG's attenuation band due to curvature. The multiplexing of the sensors is achieved by spectrally matching a series of distributed feedback (DFB) lasers to the LPGs. The versatility of this sensing garment is confirmed by it being used on six other human subjects covering a wide range of body mass indices. Just six fully functional sensors are required to obtain a volumetric error of around 6%.

Morbidity and Irish Catholic descent in Britain: an ethnic and religious minority 150 years on.

Ethnic and religious minorities often suffer disadvantages both in socio-economic status and in health. Data from the West of Scotland Twenty-07 study suggest some differences in morbidity between those descended from Irish Catholic migrants of the great emigration from 1840 onwards and others. Catholic religion of at least one parent or at birth is used here as a proxy measure to indicate Irish Catholic descent, on the basis of estimates of sensitivity and specificity in the local area. Higher proportions of "Catholics" are in manual social classes. Differences between "Catholics" and "non-Catholics" in one or more age cohorts are observed for the following aspects of health and physical development: general and physical health (self-assessed health, number of symptoms, accidents), psychological distress (depression, anxiety, number of psychosomatic symptoms), impairments and disabilities (sight, hearing, wearing dentures, disability), and physical measures (height, waist-to-hip ratio, lung function). Furthermore, for all aspects except hearing, wearing dentures and number of psychosomatic symptoms, significant differences remain after accounting for sex and social class. For each measure where a difference is observed, it is those respondents with a Catholic parent or who were born Catholic who experience poorer health or physical development. This suggests that those of Irish Catholic descent are at some disadvantage compared with the rest of the population, with respect to health as well as social class, 150 years after the start of the main migration.

Effects of reduced mouth opening capacity (trismus) on pulmonary function.

In this study, pulmonary function test data were obtained from 15 healthy volunteers and 15 patients with slightly impaired ventilation during both normal and maximally reduced opening of the mouth (trismus, intercuspal position). The aim of the study was to examine the effects of complete trismus on pulmonary function using objective and subjective parameters. In maximally reduced mouth opening, both groups showed an impairment of all subjective and objective pulmonary function test data. In healthy volunteers, the significant changes in test data (P<0.05) stimulated mild to moderate pulmonary impairment, whereas patients with an already impaired pulmonary function showed a marked deterioration of their initial respiratory condition. The results of the subjective and objective parameters examined indicate that an intercuspal position (trismus) further aggravates pulmonary functional impairment. Complete trismus can be considered a risk factor to pulmonary function in patients using mouth breathing as a primary or supportive mode of respiration.

[Respiratory muscle force and resistance in patients with SAHS. The effect of using nighttime CPAP]. / Fuerza y resistencia de los músculos respiratorios en pacientes con SAHS. Efecto de la aplicación nocturna de CPAP.

UNLABELLED: During nighttime episodes of obstructive apnea in patients with sleep apnea-hypopnea syndrome (SAHS), repeated and progressive inspiratory efforts are made. Such intense nighttime activity can have a deleterious effect on daytime function of respiratory muscles. OBJECTIVE: The objective of this study was to evaluate daytime respiratory muscle function in a group of SAHS patients before and after two months of treatment with nighttime continuous positive airway pressure (CPAP). METHODS: We enrolled 12 patients with SAHS and 10 normal subjects (control group). To evaluate respiratory muscle strength we measured maximum esophageal pressure (Pesmax), transdiaphragmatic pressure (Pdimax) and inspiratory pressure in the mouth (PM). Respiratory muscle resistance was assessed using peak pressure in the mouth (PMPeak), time of tolerance (Tlim) and maximum inspiratory pressure-time index (PTimax). We also analyzed the nighttime function of respiratory muscles during apneic episodes in 10 of the 12 SAHS patients. We propose and define an index of nighttime respiratory muscle activity (RMian) as the product of the tension-time index for the diaphragm observed at the end of nighttime apneic episodes (TTdiapnea) and the apnea-hypopnea index (AHI). RESULTS: Respiratory muscle strength was similar in the two groups and no changes were observed in SAHS patients after treatment with nighttime CPAP. However, tolerance was lower in SAHS patients (PMpeak--30%, Tlim--31% and PTimax--49%). Two months of nighttime CPAP normalized all three variables in these patients. MRian was related to percent improvement in PMpeak after treatment with nighttime CPAP in SAHS patients (r = 0.66, p < 0.04). CONCLUSION: SAHS has an adverse effect on the daytime endurance of respiratory muscles that is proportional to the increase of nighttime mechanical muscle activity. The application of nighttime CPAP is restorative, probably because it allows respiratory muscles to rest.

Effects of glucocorticoids and idebenone on respiratory function in patients with duchenne muscular dystrophy.

In Duchenne muscular dystrophy (DMD) progressive weakness of respiratory muscles leads to a restrictive pulmonary syndrome that contributes to early morbidity and mortality. Currently no curative treatment exists for DMD. In a Phase II randomized placebo-controlled study (DELPHI) in 21 DMD boys at age 8-16 years, idebenone (450 mg/d) showed trends of efficacy for cardiac and respiratory endpoints. Since the DELPHI study population comprised both glucocorticoid-naïve subjects and glucocorticoid-users, we now report a post-hoc analysis investigating the effects of glucocorticoids and idebenone on markers of respiratory weakness, particularly peak expiratory flow (PEF) percent predicted (PEF%p). Baseline values of PEF%p correlated well with the percent predicted values for maximal inspiratory mouth pressure (MIP%p), forced vital capacity (FVC%p), and forced expired volume in 1 sec (FEV1%p). Baseline PEF%p and FVC%p were significantly higher in patients on concomitant glucocorticoids compared to glucocorticoid-naïve patients. In the latter subgroup, idebenone caused a 8.0 ± 12.1% improvement in PEF%p, whilst patients on placebo declined by -12.3 ± 17.9% (P < 0.05) in the course of the 12 month study. In patients receiving concomitant glucocorticoids, PEF%p remained stable (-0.4 ± 14.6%) in the idebenone group compared to a decline by -6.2 ± 12.4% (P = 0.24) in the placebo group. Idebenone showed a trend for efficacy on FVC%p only in glucocorticoid-naïve patients. Because of the study limitations, these data are exploratory and preclude any firm conclusions. In conclusion, PEF appears to be a sensitive respiratory function parameter that could be a valid and clinically relevant endpoint in intervention studies in DMD. In DELPHI the effect size of idebenone on PEF%p was significantly larger in steroid-naive patients, possibly indicating a maximum treatment effect reached by steroids or steroid-mediated suppression of idebenone's effects. The impact of standard care glucocorticoids on respiratory function will have to be considered in the planning of future interventional trials in DMD.

Respiratory function monitoring using a real-time three-dimensional fiber-optic shaping sensing scheme based upon fiber Bragg gratings.

An array of in-line curvature sensors on a garment is used to monitor the thoracic and abdominal movements of a human during respiration. The results are used to obtain volumetric changes of the human torso in agreement with a spirometer used simultaneously at the mouth. The array of 40 in-line fiber Bragg gratings is used to produce 20 curvature sensors at different locations, each sensor consisting of two fiber Bragg gratings. The 20 curvature sensors and adjoining fiber are encapsulated into a low-temperature-cured synthetic silicone. The sensors are wavelength interrogated by a commercially available system from Moog Insensys, and the wavelength changes are calibrated to recover curvature. A three-dimensional algorithm is used to generate shape changes during respiration that allow the measurement of absolute volume changes at various sections of the torso. It is shown that the sensing scheme yields a volumetric error of 6%. Comparing the volume data obtained from the spirometer with the volume estimated with the synchronous data from the shape-sensing array yielded a correlation value 0.86 with a Pearson's correlation coefficient p<0.01.

Poluição atmosférica e função pulmonar em asmáticos: associação e interação gene-ambiente / Air pollution and pulmonary function in asthmatics: gene-environment interaction and association

Os poluentes do ar induzem o aumento de componentes inflamatórios no pulmão e redução da função pulmonar. A variabilidade na resposta pulmonar à exposição à poluição atmosférica tem sido associada a polimorfismos em genes envolvidos nas respostas inflamatórias e imunológicas à inalação destes poluentes. O objetivo deste estudo foi investigar a associação entre poluição atmosférica e a função pulmonar em crianças e adolescentes asmáticos e a potencial modificação de efeito dos polimorfismos em genes antioxidantes e inflamatórios. Trata-se de um estudo epidemiológico transversal, com 112 crianças e adolescentes asmáticos, de 6 a 14 anos de idade, no período de novembro de 2015 a dezembro de 2016, residentes no município do Rio de Janeiro. Foram coletadas células da mucosa bucal para pesquisa dos polimorfismos dos genes Glutationa S Transferase M1 (GSTM1), Glutationa S Transferase T1 (GSTT1) e Glutationa S Transferase P1 (GSTP1) e Fator de necrose tumoral A (TNF-A). As variáveis desfecho foram volume expiratório forçado no 1º segundo (VEF1), capacidade vital forçada (CVF), fluxo expiratório forçado entre 25% e 75% da CVF (FEF25-75%) e pico de fluxo expiratório (PFE). Os polimorfismos foram genotipados pela técnica de reação em cadeia da polimerase (PCR), utilizando sondas Taqman®. Modelos Lineares Generalizados foram usados e a relação entre o PM10 e O3 e o VEF1, CVF, FEF25-75% e PFE foi estimada pelo método Modelo Polinomial de Defasagem Distribuída (PDLM). A modificação de efeito dos polimorfismos genéticos foi avaliada pela inclusão dos genótipos e dos poluentes no modelo de trabalho. O aumento de 10 µg/m³ de PM10 foi associado com declínio do VEF1 no dia corrente, no primeiro dia de defasagem e no acumulado de 5 dias. Nos demais indicadores, uma associação negativa foi verificada apenas no acumulado de 5 dias. Com o incremento de 10 µg/m³ de O3, uma associação negativa foi evidenciada no quarto e quinto dia de defasagem para o VEF1 e CVF, e no quinto dia de defasagem para FEF25-75 e PFE. Em indivíduos que possuem o alelo variante do TNF-308, foi observado uma associação negativa entre PM10 e o VEF1 no dia corrente (-11,23; IC95%: -19,23, -2,45), no primeiro dia de defasagem (-5,6; IC95%: -10,16, -0,8) e no acumulado de 5 dias (-9,37; IC95%: -13,75, -4,76). A interação foi observada para o GSTT1 nulo no VEF1 no dia corrente (-11,49; IC95%; -16,26, -6,45), no primeiro dia de defasagem (-6,23; IC95%: -8,81, -3,57) e no acumulado de 5 dias (-10,88; IC95%: -13,34, -8,35) e na CVF, no dia corrente (-7,94; IC95%; -11,91, -3,8), no primeiro dia de defasagem (-4,38; IC95%: -6,48, -2,23) e no acumulado de 5 dias (-7,99; IC95%: -10,01, -5,93). ). Os indivíduos com genótipo nulo GSTM1/GSTT1 combinado apresentaram uma associação negativa significativa, no incremento de 10 µg/m³ de PM10 e VEF1 e na CVF. Estes resultados evidenciaram a associação negativa entre poluentes do ar e a função pulmonar e modificação de efeito dos polimorfismos nos genes inflamatórios e antioxidantes na associação dos poluentes atmosféricos e função pulmonar

Effects of analysis method and forcing waveform on measurement of respiratory mechanics.

The respiratory system has been shown to exhibit nonlinear mechanical properties in the frequency (f) range of normal breathing, manifested by tidal volume (Vt) dependence. Calculations of respiratory system resistance (R) and elastance (E) from pressure-flow measurements during external forcing at a given f may be ambiguous, especially if non-sinusoidal forcing waveforms are used. We evaluated the degree to which R and E depended upon: (1) analysis method (Fourier transform, multiple regression and pressure-volume loop analysis) and; (2) shape of the forcing waveform (sinusoidal, quasi-sinusoidal and step). We measured pressure and flow at the mouth of 5 healthy, awake subjects, relaxed at functional residual capacity, during forcing with the three different waveforms in the normal range of f (0.2-0.6 Hz) and Vt (250-750 ml). During sinusoidal forcing, E and R were not affected by analysis method (P greater than 0.2). With Fourier transform and multiple regression, E was not affected by waveform shape (P greater than 0.05); with loop analysis, E was slightly (less than 10%) higher during quasi-sinusoidal and step forcing than during the sine (P less than 0.05). R was least affected by waveform shape with Fourier transform. We conclude that, in the f and Vt range of normal breathing: (1) respiratory system impedance is 'quasi-linear,' i.e. despite dependencies of R and E on Vt, non-linearities are not large enough to restrict interpretation of R and E at a given f and Vt; (2) it may be possible to measure R and E using non-sinusoidal forcing waveforms available on most clinical ventilators, incurring only modest error.

Accuracy and sensitivity of the interrupter technique for measuring the response to bronchial challenge in normal subjects.

The interrupter technique is a non-invasive method for measuring airway calibre. Since the calculation of interrupter resistance (Rint) is critically dependent upon the analysis of the mouth pressure/time (Pmo(t)) curve obtained after flow interruption, we wanted to assess the relative merits of four different analyses of Pmo(t) curves, obtained under basal conditions and following methacholine-induced airway narrowing, in 10 healthy adults. Four methods of analysing the Pmo(t) curves were used to calculate Rint values: RintC-a smooth curve fit with back-extrapolation; RintL-two-point linear fit with back-extrapolation; RintEO-calculated from the pressure change after the post-interruption oscillations had decayed (end-oscillation); and RintEI-calculated from the pressure change at the end of the period of interruption. The airway response measured with the four Rint methods was compared with plethysmographic airway resistance (Raw). The sensitivity of the methods was determined by calculating a sensitivity index (SI), the change in resistance after challenge expressed in multiples of baseline standard deviation. Values of RintC were similar to Raw values under all conditions. Resistance values from the remaining Rint methods significantly exceeded Raw (mean basal difference: 0.13-0.34 kPa.l-1 x s; mean difference after challenge: 0.12-0.42 kPa.l-1 x s. Raw was the most sensitive method for detecting bronchoconstriction (doubling of Raw was equivalent to SI of 10.5). Of the Rint methods, RintEI gave the highest sensitivity index (SI = 3.1), with a 42% mean change; RintC produced the greatest proportionate change after challenge (55%), but with a lower SI (2.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Water loss without heat flux in exercise-induced bronchospasm.

We identified inspired gas conditions that result in no net respiratory heat loss, an isenthalpic condition, but induce a mucosal loss of water. Inspired gas at 37 degrees C with 47 mm Hg water vapor pressure, 56 degrees C with 38 mm Hg; and 78 degrees C with 27 mm Hg has the same heat content as fully saturated air at body temperature. In four normal subjects hyperventilating at a minute ventilation of 30 times their FEV1 for 6 min, expired temperatures at the mouth averaged 39 degrees, 43 degrees, and 43 degrees C for the three conditions. Retrotracheal esophageal temperatures did not fall in any subject, thereby demonstrating the absence of significant airway cooling. Nine subjects with exercise-induced bronchospasm were tested under the same conditions. Baseline functions showed an FEV1 of 85 +/- 10% of predicted (mean +/- SD), FVC, 98 +/- 13% of predicted, and FEV1/FVC, 79 +/- 4% of predicted. The asthmatic subjects demonstrated postchallenge mean falls in FEV1 of 3.4%, 6.2%, and 10.1% for the three conditions, with bronchospasm increasing as the temperature of the inspired air increased (p = 0.001). The amount of respiratory water lost from the respiratory mucosa significantly correlated with the resultant bronchospastic response as measured by the fall in FEV1 (p = 0.017), but the net respiratory heat lost did not significantly correlate (p = 0.113). This study demonstrates that bronchospasm can be induced without significant respiratory heat loss or airway cooling and suggests that it is proportional to the amount of water lost from mucosal surfaces.

Effects of a filter at the mouth on pulmonary function tests.

The aim of this study was to verify whether the increase of resistance to airflow using a filter at the mouth could determine significant systematic errors of measurement or change the diagnostic performance in a respiratory physiology laboratory. The effect of the new filter Spirobac (DAR Spa, Italy) was assessed on out-patients referred to our laboratory for routine functional evaluation. The following tests were performed: maximal expiratory flow-volume curve, plethysmographic lung volume and airway resistance, bronchodilator test, and methacholine challenge test. Each test was performed randomly, twice with the filter and twice without. Significant differences between measurements with and without filter were found for forced vital capacity, forced expiratory volume in one second, airway resistance, and specific airway conductance (sGaw). These differences were unrelated to the average values of the measurements, except for sGaw. The limits of agreement were within the range of intraindividual short-term repeatability for almost all of the function indices. The overall concordance between tests performed with and without filter was 78% for bronchodilator test and 53% for methacholine test. However, in all the cases but one, the concordance of the methacholine test was inside the short-term repeatability. We conclude that the filter Spirobac has a statistically significant effect on the results of some pulmonary function tests. However, this is not considered to be clinically significant, since the changes due to the filter were within the intraindividual variability of repeated measurements for almost all the function indices and no appreciable classification error was found in diagnostic tests.

Reference values of maximal respiratory mouth pressures: a population-based study.

The aim of our study was to measure values of maximal inspiratory (MIP) and expiratory (MEP) mouth pressures in 625 (266 male, 359 female) clinically and functionally normal subjects drawn out of a sample representative of the general population. MEP (near TLC and FRC) was found to be significantly higher when compared with MIP (near RV and FRC), and pressures in male subjects were significantly higher than those in female subjects. MEP values at TLC and FRC were found to be closely related, as were values of MIP near RV and near FRC. Among the tested body-size variables, body surface area (BSA) for all parameters had the highest degree of correlation. Stepwise linear regression analysis was performed to define the equation of normality for all four parameters, employing BSA, sex, age, and relative interaction terms. R2 values, although the variables employed for the equations were highly significant, were relatively low and didn't fully explain the source of variability. The influence of age was smaller than the influence of BSA, although age did reduce the unexplained variance in MEP and MIP. These results confirm that the most useful employment of MIP and MEP is to monitor their changes in each patient, but they point out, however, the usefulness of reliable reference equations.

Influence of neck muscles on mouth pressure response to cervical magnetic stimulation.

Measurement of mouth pressure (Pm) in response to electrical phrenic nerve stimulation (Es) provides a simple noninvasive means to assess diaphragm function. An even simpler measure would be to use the Pm twitch response (Pm,t) to cervical magnetic stimulation (CMS) rather than to Es. Because CMS coactivates the diaphragm and inspiratory neck muscles (INM), CMS-Pm,t accurately reflects diaphragm function only if the corresponding INM contraction does not produce inspiratory pressures by itself. In patients with recent-onset bilateral diaphragm paralysis, it has been demonstrated that CMS-Pm,t was indeed zero; however, INM hypertrophy could change this situation and lead CMS-Pm,t to overestimate the performance of the diaphragm. To address this issue, we studied nine patients with amyotrophic lateral sclerosis (ALS) who had evidence of diaphragmatic paralysis and compensatory hypertrophy and hyperactivity of inspiratory neck muscles. The response to CMS was described in terms of diaphragm electromyogram (EMG), Pm, and abdominal (AB) and rib cage (RC) motion. No EMG response to CMS could be observed in most cases, and CMS was always associated with AB paradox. Nevertheless, a negative Pm,t swing was recorded with an amplitude of -2.6 +/- 1.0 cm H2O (mean +/- SD). We conclude that inspiratory neck muscle hypertrophy can significantly influence the Pm response to CMS. This should be taken into account when using the CMS-Pm combination in patients with possible chronic diaphragm dysfunction.

Noninvasive assessment of inspiratory muscle function during exercise.

The use of esophageal and gastric balloons limits measurement of the tension-time index of inspiratory muscles (TTI) during exercise. The aim of this study was to assess whether a noninvasive tension-time index, TT(0.1), given by P(0.1)/PI(max) x TI/Ttot (where P(0.1) is mouth occlusion pressure, PI(max) is maximal inspiratory pressure, and TI/Ttot is duty cycle) could reliably assess TTI during exercise. In seven healthy young men and nine patients with COPD we measured TT(0.1) and TTI (i.e., Pes/Pes(max) x TI/Ttot where Pes is mean esophageal pressure and Pes(max) is maximal static Pes) at rest and during an incremental exercise test. A significant linear correlation (p < 0.02) was found between TT(0.1) and TTI in all normal subjects and patients with COPD. An equation for estimating TTI from TT(0.1) was established for each group. In the normal subjects there was good agreement between estimated and observed data. In five additional normal males studied prospectively, the agreement was also satisfactory and reproducible. In the COPD patients the agreement was poor. In conclusion, in young healthy subjects the changes in TT(0.1) during exercise reflect the changes in TTI, allowing satisfactory estimation of TTI from noninvasive measurements of TT(0.1).