Maximal inspiratory flow rates in patients with COPD.

OBJECTIVES: To assess the relevance of maximal inspiratory flow rates (MIFR) in the assessment of airway obstruction in COPD. SETTING: University teaching hospital. PARTICIPANTS: Ten consecutive COPD patients (O group; mean [+/- SD] age, 58.5+/-8.3 years) and 10 matched healthy subjects (H group; mean age, 58.7+/-7.4 years). MEASUREMENTS: Lung volumes, FEV(1), specific airway conductance, single-breath lung diffusing capacity, MIFR, and maximal expiratory flow rates (MEFR). RESULTS: Mean FEV(1)/vital capacity (VC) was 74.7% in the H group and 37.8% in the O group (p<0.001). Total lung capacity was higher (p<0.001) in the O group compared with the H group. Lung diffusing capacity was less than half in the O group compared with the H group (p<0.001). MEFR at all lung volumes were lower in the O group (p<0.001). MIFR were comparable in the two groups, except at 25% inspired VC, where MIFR were lower in the O group (p< 0.05). CONCLUSION: MIFR are less sensitive than MEFR to detect airway obstruction in COPD patients. Yet, the interest of MIFR lay in the possibility to separate intrinsic from extrinsic involvement of airways. A normal MIFR associated with low MEFR, as in the present study, suggests either a lack of parenchymal support, an increased collapsibility of the airways, or a reversible peripheral airway narrowing. A fixed, generalized airway narrowing would be associated with a decrease of both MIFR and MEFR.

Lung function study and diffusion capacity in anorexia nervosa.

STUDY OBJECTIVES: In humans, malnutrition alters the respiratory system in different ways. It impairs the ventilatory drive, decreases respiratory muscle strength and reduces immune competence. In addition, typical emphysema-like changes were demonstrated in starved animals. The presence of emphysema has never been demonstrated in starved humans. Our objective was to investigate whether pulmonary emphysema occurs in anorexia nervosa by means of a pulmonary function study. POPULATION AND METHOD: We examined 24 women aged between 14 and 38 years (nine smokers). We studied the lung function including lung volumes, ventilatory capacity, maximal respiratory pressures and transfer factor, as well as PaO2. RESULTS: All respiratory tests were within normal limits with the exception of decreased maximal inspiratory (59% of predicted values) and expiratory pressures (35%), and increased residual volume (162%). Diffusion capacity (98.1 +/- 16.2%) and transfer coefficient (98.4 +/- 16.2%) were also normal. The diffusion coefficient was lower in current smokers than in those who had never smoked (P < 0.01), a difference similar to that calculated from existing reference values for transfer factor for smokers and nonsmokers. CONCLUSION: In anorexia nervosa, pulmonary function tests are within normal limits with the exception of maximal pressures and residual volume. Diffusion capacity is not decreased. The present results within the limitations of the used method are not compatible with the hypothesis of starvation-induced pulmonary emphysema.

In long-term smokers and former smokers the bronchodilator response is not related to the fall in FEV.

BACKGROUND: Cigarette smoking is the cardinal cause of chronic obstructive pulmonary disease (COPD), but only a relatively small percentage of smokers are developing clinically overt disease, suggesting, therefore, that other risk factors than smoking are involved. Several studies have shown that the bronchodilator response (BR) is related to the progress of COPD, as assessed by the fall in forced expiratory volume in 1 s (FEV(1)). However, the relationship between BR and fall in FEV(1), is a disputed one. OBJECTIVE: To assess the relationship between BR and fall in FEV(1) in a group of long-term smokers and ex-smokers who were 60 years old on the average. METHODS: Questionnaire, spirographic tests and BR were assessed in 56 smokers and ex-smokers of mean age 62.5 +/- (SD) 2.7 years at the end of a 13-year follow-up period. BR was expressed as a percentage change of the prebronchodilator value ('% initial') and as a percentage change of predicted value ('% predicted'). RESULTS: The FEV(1)/VC vital capacity was 68.9 +/- 7.6% at the start and 64.5 +/- 11.3% at the end of the study. The average fall in FEV(1) over 13 years was 26 +/- 25 ml/year. The FEV(1) increased after albuterol on the average with 5.9 +/- 6.6%, 4.5 +/- 3.9% of predicted, and the vital capacity with 2.5 +/- 6.5%, 2.3 +/- 6.4% of predicted. BR and fall in FEV(1) were correlated: the greater the BR, the more rapid the fall in FEV(1) (r = 0.4 and p < 0.01 for FEV(1)% and r = 0.3 and p < 0.05 for FEV(1) predicted). However, when adjusting for prebronchodilator FEV(1), the BR was no more related to the fall in FEV(1) (r = 0.15, p > 0.05). CONCLUSIONS: In long-term smokers and ex-smokers, the BR measured at the end of the follow-up period was correlated with the fall in FEV(1). However, after adjusting for prebronchodilator FEV(1) values, BR was no more related to the decline in FEV(1). The BR appears not to be associated with the development of COPD.

Expiratory flow limitation in awake sleep-disordered breathing subjects.

Increased upper airways (UA) collapsibility has been implicated in the pathogeny of sleep-disordered breathing (SDB). An increased UA instability during expiration has recently been shown in healthy subjects. The present study assessed UA collapsibility in SDB patients by applying negative pressure during expiration. Full-night polysomnography was performed in 16 subjects (all snorers) with a wide range of SDB, and in six healthy control subjects. Physical examination, spirometry, and maximal inspiratory and expiratory flow rates were within normal limits for all 22 subjects. Negative expiratory pressure (NEP) (-5 cmH2O) was applied during quiet breathing in seated and supine position. Flow limitation (FL) during NEP was expressed as the percentage of tidal volume during which expiratory flow was less than or equal to the flow recorded during quiet breathing (%FL). The mean desaturation index (DI) of the 16 subjects was 27.3+/-26.4 (+/-sD) and the average FL in supine position was 38.4+/-37.9%. A close correlation between %FL supine during wakefulness and DI during sleep (r=0.84, p<0.001) was found. All obstructive sleep apnoea subjects had >30%FL supine. There was no FL in the six control subjects. In conclusion, negative expiratory pressure application during expiration appears to be a useful, noninvasive method for the evaluation of subjects with sleep-disordered breathing. Present results suggest that upper airway collapsibility can be detected in these subjects during wakefulness.

Influence of gas density on simulated snoring.

According to a recent theoretical model, snoring is related to instability of the upper airway (UA). Factors promoting UA instability include increased gas density. The aim of this study was to test the influence of gas density on simulated snoring production and supraglottic resistance. Supraglottic pressure and flow rate (V') were measured in 10 healthy seated subjects during simulated snoring. Subjects breathed three different gas mixtures: Helium-oxygen, He 79%-O2 21% (He-O2); air; and sulphur hexafluoride-oxygen, F6S 79%-O2 21% (F6S-O2) administered in a random order. Supraglottic resistance (Rsg) was measured on its linear range during quiet breathing and V' was measured at the onset and middle of snoring. Linear Rsg increased and V' conversely decreased with gas density. These data are in agreement with predictions of a mathematical model of the upper airway showing that snoring occurs at lower flow rates when gas density is increased.

Pulmonary gas exchange in life-long nonsmoking patients with diabetes mellitus.

In a companion paper, we have found that the alveolar epithelial basal lamina, endothelial basal lamina and both fused were significantly thicker in 6 autopsied diabetics than in 6 control subjects. The purpose of the present work was to assess whether these lesions have detrimental effects on gas exchange. We investigated 20 life-long nonsmoking subjects: 10 healthy subjects and 10 insulin-dependent diabetics. All of them had one to four diabetic complications of the following organs: kidney, retina, nerves or arteries. Their pulmonary gas exchange and their transfer factor were measured at rest and during two levels of submaximal exercise. Spirometric data, specific airway conductance, transfer factor, transfer coefficient, oxygen consumption and arterial blood gases were normal and almost identical in both groups. In conclusion, the thickening of lung basal laminae has no detrimental effect on pulmonary gas exchange in insulin-dependent diabetics with peripheral complications.

Effect of CPAP on breathlessness perception in healthy subjects during methacholine induced bronchoconstriction.

Application of continuous positive airway pressure (CPAP) in asthmatic patients decreases breathlessness (B). The effect of CPAP on induced bronchoconstriction was studied in healthy subjects. The changes in B were related to changes in lung function indices. In nine healthy volunteers, males aged 20-27 years, acute bronchoconstriction was induced by inhalation of 1 to 128 mg/ml methacholine (M). CPAP (0.5 kPa) was then applied for 1 min. It was followed by inhalation of albuterol. Forced expiratory volume in 1 s (FEV1) and vital capacity (VC) were measured by spirometry and end expiratory lung level (EELL), to derive inspiratory capacity (IC), by inductive plethysmography. B was assessed by Borg scale. After the maximal concentration of M, FEV1 decreased by 14% (p < 0.01) as compared to the control values and Borg score (BS) increased to 2.4 (p < 0.01). In 7 out of 9 subjects we found a significant (p < 0.05) correlation between the changes in FEV1 and BS. BS decreased during CPAP (p < 0.01) and it further decreased significantly after albuterol. There was no correlation between the changes in IC and FEV1 during bronchoconstriction, or between IC and BS during CPAP. In conclusion, in healthy subjects with induced bronchoconstriction CPAP decreased significantly BS, which was further improved by inhalation of albuterol. B was related to changes in FEV1 but not in IC.

Identification of smokers susceptible to development of chronic airflow limitation: a 13-year follow-up.

BACKGROUND: Cigarette smoking is the cardinal cause of COPD, but only a relatively small percentage of smokers have development of clinically overt disease. OBJECTIVES: To identify high-risk subjects and to assess the prognostic significance of "small airways" tests. SETTING: University teaching hospital. SUBJECTS: Fifty-six smokers and ex-smokers of mean age 62.5 years (SD, 2.7) with a smoking history of 40.6 (18.9) pack-years were studied at the end of a 13-year follow-up period. MEASUREMENTS: Questionnaire and lung function tests, including static and dynamic lung volumes, airway resistance, maximal expiratory flow rates, and small airways tests, such as nitrogen slope of the alveolar plateau (N2 slope) and closing volume. RESULTS: Eighty-two percent of subjects with a normal FEV1/vital capacity (VC) ratio at the start of the study (half of them with abnormal results of small airways tests) still had a normal FEV1/VC ratio 13 years later. In the remainder, all but one had final FEV1/VC values >60%. About 80% of subjects with a decreased FEV1/VC at the start (subjects with airflow obstruction) reached at the end of study lower than predicted FEV1/VC values. Only about 10% of these subjects showed an accelerated loss of FEV1, reaching end FEV1/VC values of <45%. Initial N2 slope predicted about 80% of end FEV1 values. CONCLUSION: Middle-aged smokers are at no evident risk of functional deterioration if their FEV1/VC ratio is normal. This is so even if results of small airways tests are abnormal. A decreased FEV1/VC ratio has no serious implications in itself. Only an associated high N2 slope adds the necessary information to predict a low FEV1. Present data suggest that a subgroup of smokers in their 50s, characterized by a low FEV1/VC ratio and a high N2 slope, are probably the susceptible smokers at high risk for development of COPD.

Validation of cardiac echocardiography for measuring cardiac output to be applied for the multiple inert gas elimination technique.

The multiple inert gas elimination technique (MIGET) is being increasingly used in respiratory physiology and pathophysiology. Six inert gases are given as an intravenous infusion then measured in samples of expired air and mixed arterial and venous blood. This requires right-sided catheterization, a procedure that is sometimes ethically inappropriate. The present article reports a method in which inert gas levels in mixed venous blood were calculated, rather than measured, using Fick's law. Echocardiography was used to measure arterial inert gas levels and cardiac output. The method was validated in 11 men scheduled to undergo coronary bypass surgery. Cardiac output was either calculated based on biometrical (C) data or measured using four different methods in random order, namely Fick's law with oxygen (FiO2) or the inert gases (FiIG) as the tracers, thermodilution (TH), and echocardiography (E). Cardiac output values in L.min-1 (mean +/- SD) were as follows: C, 4.99 +/- 0.39; FiO2, 5.44 +/- 0.86; FiIG, 5.55 +/- 0.92; TH, 5.77 +/- 0.88; and E, 5.53 +/- 0.64. No significant differences were found among the four measured cardiac output values, of which the mean was 5.57 +/- 0.70 L/min, a value that was significantly higher than the calculated value. This difference is probably ascribable to the use of dopamine, dobutamine, or epinephrine in six of the 11 patients. A 1 L/min-1 cardiac output error, in either direction, was found to have a marked influence on the distribution of alveolar perfusion at various VA/Q ratios. Conversely, as expected, ventilation distribution was not influenced by cardiac output. In conclusion, echocardiography provides satisfactory cardiac output estimations using the MIGET except in patients with septal hypertrophy, subaortic membranes, a mitral valve prosthesis, or a mitral valve ring.

Effect of alveolar volume on the interpretation of single breath DLCO.

Single-breath carbon monoxide diffusing capacity in the whole lung (DLCO) and per unit alveolar volume (DLCO/VA), as expressed in percentage of normal values, gave discordant results when VA of the patients was abnormal. It was hypothesized that normal reference values were inappropriate to interpret data collected in such patients. To substantiate this hypothesis, DLCO and DLCO/VA were measured in four groups: (1) normal volunteers in whom both indices were measured at five different VA; (2) patients with high VA; (3) emphysematous patients; and (4) patients with diffuse interstitial lung diseases (DILD). In normal subjects, DLCO increased and DLCO/VA decreased with VA. In patients with overinflated lungs, the percentage of DLCO was more increased than DLCO/VA. In the emphysematous patients, both indices were equally decreased. In patients with DILD, DLCO was significantly more decreased than DLCO/VA in those suffering from a restrictive pattern. Theoretical values were re-calculated taking into account their true VA and using the relationships observed between DLCO, DLCO/VA and VA. The divergences between DLCO and DLCO/VA were strongly minimized. Therefore, the authors suggest the need to correct theoretical formulas in the presence of a restrictive pattern.

Integrin upregulation on sputum neutrophils in smokers with chronic airway obstruction.

To determine the relationship between the expression of leukocyte-specific integrins in the airways and the airway obstruction in smokers, we analyzed hypertonic saline-induced sputum in 33 male subjects, age 64.7 +/- 0.5 yr (mean +/- SEM), with a smoking history of 12 to 94 pack-years, at the end of a 15-yr follow-up study. Average FEV1/VC ratio was 69 +/- 1% at the beginning of the study and 66 +/- 2% at the end of the follow-up period, and annual decline of FEV1 was 20 +/- 3 ml/yr. Fourteen individuals exhibited airway obstruction as assessed by a FEV1/VC ratio lower than 63.3%. Differential leukocyte count was performed on cytospin preparations and the expression of integrin alpha (CD11a, CD11b, CD11c) and beta (CD18) chains was assessed on granulocytes and mononuclear cells by immunocytology. The numbers of neutrophils expressing CD11b and CD18, but not CD11c or CD11a, were increased in the subjects with airway obstruction compared with those without airway obstruction. CD11b- and CD18-positive neutrophils were negatively correlated with FEV1/VC ratio (p < 0.01). No significant correlations were found between CD11a-, CD11b-, CD11c-, CD18-positive mononuclear cells and lung function measurements. In conclusion, our results suggest that leukocyte-specific integrin CD11b/CD18 expressed on sputum polymorphonuclear leukocytes represents a marker for the smokers who develop chronic airway obstruction.

Expiratory flow limitation during sleep in heavy snorers and obstructive sleep apnoea patients.

Inspiratory flow limitation (FL) during sleep has previously been reported both in obstructive sleep apnoea (OSA) patients and heavy snorers (HS). Recent results from this laboratory have shown the occurrence both of inspiratory and expiratory flow limitation during muscular relaxation in awake healthy subjects and OSA patients. In this study, we have investigated whether expiratory flow limitation occurs during sleep in heavy snorers and in patients with OSA. We studied four nonapnoeic, heavy snorers and five OSA patients. Airflow was measured with a pneumotachograph attached to a tight-fitting mask, and supraglottic pressure with a catheter placed at the supraglottic level. Scoring for flow limitation was achieved by visual inspection of 200 breaths recorded during sleep. About 20% of the respiratory cycles presented isolated inspiratory flow limitation. Approximately the same percentage was observed in heavy snorers and OSA patients. Isolated expiratory flow limitation was less frequently recorded. Coupled inspiratory and expiratory flow limitations were more numerous, especially in heavy snorers. We conclude that both in heavy snorers and obstructive sleep apnoea patients, inspiratory flow limitation is associated with expiratory flow limitation. This suggests that upper airway obstruction during sleep is both an inspiratory and expiratory event.

Tracheal distensibility in cystic fibrosis.

Size and distensibility of large airways have important implications for flow limitation and the efficacy of coughing. From radiological and functional data, some authors have suggested an increased size and distensibility of the trachea in cystic fibrosis (CF). Using computed tomography (CT) we compared size and distensibility of the trachea in 5 cystic fibrosis patients and five age- and height-matched healthy volunteers. Tracheal cross-sectional area was measured 25 mm below the cricoid cartilage. CT recordings were made at functional residual capacity, at 0 and +20 cmH2O mouth pressure. Inductive plethysmography was used to check that during these manoeuvres lung volume did not change and that the glottis remained open. Tracheal cross-sectional area and derived indices of tracheal distensibility were similar in the two groups. This study does not support the concept of an increased size and distensibility of the trachea in cystic fibrosis.

Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils.

BACKGROUND: Smoking may cause inflammation of the airways and impairment of lung function. To determine the relationship between the type and degree of airways inflammation and the decline in lung function, leucocytes in the sputum of smokers and ex-smokers were examined. METHODS: Forty six smokers and ex-smokers of median age 64 years (25%; 75% percentiles 62;66) with a smoking history of 40.1 (31.7;53) pack years were studied with lung function tests and a questionnaire at the end of a 15 year follow up period. Sputum was induced by inhalation of hypertonic saline and differential leucocyte counts were performed on cytospin preparations. RESULTS: Adequate sputum samples were obtained in 38 subjects (78%). The ratio of forced expiratory volume in one second (FEV1) to vital capacity (VC) was 67.1 (60; 72)% and the annual decline in FEV1 was 19.4 (12;30) ml/year. Subjects with airways obstruction (FEV1/VC < 63%) had more neutrophils (77 (50;86)%) than those without airways obstruction (60 (43;73)%). The percentage of neutrophils was also significantly greater (77 (62;85)%) in those with chronic expectoration than in those without expectoration (57 (45;75)%. Increased levels of neutrophils in the sputum were correlated with a rapid decline in FEV1 over the 15 year follow up period. CONCLUSIONS: Airways obstruction and chronic expectoration, as well as accelerated decline in lung function, are associated with increased numbers of neutrophils in the sputum of smokers and ex-smokers which suggests that neutrophilic inflammation of the airways may be involved in the pathogenesis of chronic obstructive pulmonary disease.

Effect of preinspiratory maneuver on the single-breath DLCO.

We have observed in some patients with pulmonary disease and normal subjects that the difference between two successive measurements for single-breath DLCO amounted to 10%. By scrutinizing data from these subjects, we observed that they spontaneously changed their preinspiratory maneuver just before inhaling the test gas mixture. The purpose of the present work is to assess the influence of five different preinspiratory maneuvers on DLCO. Nine healthy males were investigated. They performed at random the five following maneuvers: (A) rapid exhalation from functional residual capacity (FRC) to residual volume (RV), (B) rapid exhalation from FRC to RV and long apnea at RV, (C) rapid exhalation from FRC to RV and short apnea at RV, (D) slow exhalation at a constant speed from FRC to RV, and (E) curvilinear exhalation from FRC to RV. The DLCO values after maneuver B were higher than those after the four other maneuvers; there was a significant relationship between DLCO and the duration of the preinspiratory maneuver. The data are best explained by an alteration in the distribution of the inspired gas mixture to areas with different diffusing capacities. In conclusion, the preinspiratory maneuvers must be standardized in order to improve the reproducibility of the single-breath DLCO measurements.

Expiratory supraglottic obstruction during muscular relaxation.

Some reports have suggested occurrence of expiratory upper airway narrowing in patients with obstructive sleep apnea (OSA) during sleep and in awake humans during respiratory muscles relaxation. This is compatible with the hypothesis that upper airway muscles are activated during expiration. We studied five healthy volunteers and four patients with OSA in a tank respirator (Emerson; Cambridge, Mass). Supraglottic pressure (Psg) was measured with a catheter with the tip at the retroepiglottic level, tidal volume with an inductance plethysmograph and airflow with a pneumotachograph at the mouth. Diaphragmatic electromyogram was recorded with an esophageal bipolar electrode. Measurements were done at -30 cm H2O. Subjects were asked to breathe in phase with the respirator and then asked to breathe in phase with the respirator and then to relax their muscles. During muscular relaxation, there was supraglottic obstruction and flow limitation. This was observed during both inspiration and expiration. Upper airway obstruction was more severe in patients with OSA than in healthy subjects. In two healthy volunteers, fiberoptic bronchoscopy showed a wide-open oropharyngeal isthmus during active breathing that narrowed during muscular relaxation. This was true during both inspiration and expiration. We conclude that muscular relaxation is associated with upper airway narrowing and flow limitation occurring during both inspiration and expiration. We suggest that to preserve an open upper airway, airway muscles have to be activated during both inspiration and expiration.

Bronchodilator effect of inhaled nitric oxide in healthy men.

Studies in animals have shown that inhalation of nitric oxide (NO) either reduced pulmonary resistance after an induced bronchospasm or protected animals from bronchoconstriction. To evaluate whether NO inhalation (80 parts per million) influences basal bronchial tone or reverses methacholine-induced bronchospasm, we determined specific airway conductance (SGaw) as a measure of airway caliber in seven healthy men. After methacholine-induced bronchoconstriction NO increased SGaw by 23% (p < 0.05). One week later, NO inhalation did not change baseline SGaw values. However, albuterol inhaled after NO, or on a separate day, significantly increased SGaw (p < 0.05). The bronchodilator effect of NO in men with methacholine-induced bronchospasm is much less than that reported in animals or that regularly observed in asthmatic patients after the inhalation of beta-sympathomimetic drugs.