Giorgio Scano

Sputum analysis, bronchial hyperresponsiveness, and airway function in asthma: Results of a factor analysis

BACKGROUND Recent studies have shown weak associations among FEV1, bronchial hyperresponsiveness (BHR), sputum eosinophils, and sputum eosinophil cationic protein (ECP), suggesting that they are nonoverlapping quantities. The statistical method of factor analysis enables reduction of many parameters that characterize the disease to a few independent factors, with each factor grouping associated parameters. OBJECTIVE The purpose of this study was to demonstrate, by using factor analysis, that reversible airway obstruction, BHR, and eosinophilic inflammation of the bronchial tree, as assessed by cytologic and biochemical analysis of sputum, may be considered separate dimensions that characterize chronic bronchial asthma. METHODS Ninety-nine clinically stable patients with a previous diagnosis of asthma underwent spirometry, sputum induction, and histamine inhalation tests. RESULTS Most patients were nonobstructed (FEV1, 91% +/- 20%); a low level of bronchial reversibility (FEV1 increase after beta2 -agonist, 7.8% +/- 9.2%) and BHR (histamine PC20 FEV1 geometric mean, 0.98 mg/mL) were found. Sputum eosinophil differential count (12.4% +/- 17.7%) and sputum ECP (1305 +/- 3072 microg/mL) were in the normal range of our laboratory in 38 and 22 patients, respectively. Factor analysis selected 3 different factors, explaining 74.8% of variability. Measurements of airway function and age loaded on factor I, PC20 FEV1 and beta2 -response loaded on factor II, and sputum ECP and eosinophils loaded on factor III. Additional post hoc factor analyses provided similar results when the sample was divided into 2 subgroups by randomization, presence of airway obstruction, degree of BHR, percentage of sputum eosinophils, or concentration of sputum ECP. CONCLUSIONS We conclude that airway function, baseline BHR, and airway inflammation may be considered separate dimensions in the description of chronic asthma. Such evidence supports the utility of routine measurement of all these dimensions.

In vivo ultrasound assessment of respiratory function of abdominal muscles in normal subjects

Ultrasonography has recently been proposed for assessing changes in thickness and motion of the diaphragm during contraction in humans. Data on ultrasound assessment of abdominal muscles in humans are scarce. We therefore investigated the changes in thickness and the relevant mechanical effects of abdominal muscles using this technique during respiratory manoeuvres in normal subjects. We evaluated the thickness of the abdominal muscle layers in six normal male subjects (aged 26-36 yrs) using a 7.5 MHz B-mode ultrasound transducer. Gastric (Pg) and mouth pressures, muscle thickness of external oblique (EO), internal oblique (IO), transversus abdominis (TA) and rectus abdominis (RA) were assessed at functional residual capacity (FRC), residual volume (RV), total lung capacity (TLC), during progressive (PEEs) and maximal expiratory efforts (MEEs) against a closed airway and during homolateral (HTR) and contralateral (CTR) trunk rotation. Abdominal muscle thickness was found to be reproducible (coefficient of variation and two-way analysis of variance). Compared to FRC, the thickness of IO, TA and RA significantly increased at RV and during MEEs, whereas EO remained unchanged; at TLC, the thickness of IO and TA significantly decreased. During PEEs, a significant relationship between increase in Pg and TA thickness was observed in all subjects, the thickness of the other abdominal muscles being inconsistently related to Pg. Finally, a significant increase in the thickness of IO and EO was found during HTR and CTR, respectively. We conclude that during maximal expiratory manoeuvres, transversus abdominis, internal oblique and rectus abdominis thickened similarly. Transversus abdominis seems to be the major contributor in generating abdominal expiratory pressure during progressive expiratory efforts. External oblique seems to be preferentially involved during trunk rotation. These results suggest the possible value of studying the abdominal muscles by ultrasonography in various respiratory disorders.

Role of sputum differential cell count in detecting airway inflammation in patients with chronic bronchial asthma or COPD.

BACKGROUND: Sputum may provide an alternative source of bronchial cells to investigate characteristics of airway inflammation and its functional correlates in patients with asthma or chronic obstructive pulmonary disease (COPD). METHODS: Two groups of clinically stable patients were studied: a group of 43 patients with mild or moderate asthma and a group of 18 patients with COPD. Twenty normal subjects formed a control group. Sputum production was either spontaneous or induced with inhaled hypertonic saline for five minute periods for up to 20 minutes. The concentration of saline was increased at intervals of 10 minutes from 3% to 4%. Plugs from the lower respiratory tract were selected for differential counting in cytocentrifugation preparations. Bronchial provocation tests were performed by inhaling progressive concentrations of histamine from a DeVilbiss 646 nebuliser and the concentration of histamine which caused a 20% fall in the forced expiratory volume in one second (FEV1) was calculated (PC20FEV1). RESULTS: Neutrophils predominated in the sputum of subjects with COPD while eosinophils predominated in the sputum of those with chronic asthma. However, in 28% of asthmatic subjects an increased percentage of neutrophils was found. In asthmatic patients the differential count of eosinophils was inversely related to the FEV1, FEV1/VC, and bronchial hyperresponsiveness, and directly related to clinical scores. CONCLUSIONS: The cellular profile of sputum in normal subjects and in patients with asthma and COPD is different. The concentration of eosinophils in the sputum correlates with the severity of asthma.

Exercise training improves exertional dyspnea in patients with COPD: evidence of the role of mechanical factors.

BACKGROUND To our knowledge, no data have been reported on the effects of exercise training (EXT) on central respiratory motor output or neuromuscular coupling (NMC) of the ventilatory pump, and their potential association with exertional dyspnea. Accurate assessment of these important clinical outcomes is integral to effective management of breathlessness of patients with COPD. MATERIAL AND METHODS Twenty consecutive patients with stable moderate-to-severe COPD were tested at 6-week intervals at baseline, after a nonintervention control period (pre-EXT), and after EXT. Patients entered an outpatient pulmonary rehabilitation program involving regular exercise on a bicycle. Incremental symptom-limited exercise testing (1-min increments of 10 W) was performed on an electronically braked cycle ergometer. Oxygen uptake (O(2)), carbon dioxide output (CO(2)), minute ventilation (E), time, and volume components of the respiratory cycle and, in six patients, esophageal pressure swings (Pessw), both as actual values and as percentage of maximal (most negative in sign) esophageal pressure during sniff maneuver (Pessn), were measured continuously over the runs. Exertional dyspnea and leg effort were evaluated by administering a Borg scale. RESULTS Measurements at baseline and pre-EXT were similar. Significant increase in exercise capacity was found in response to EXT: (1) peak work rate (WR), O(2), CO(2), E, tidal volume (VT), and heart rate increased, while peak exertional dyspnea and leg effort did not significantly change; (2) exertional dyspnea/O(2) and exertional dyspnea/CO(2) decreased while E/O(2) and E/CO(2) remained unchanged. The slope of both exertional dyspnea and leg effort relative to E fell significantly after EXT; (3) at standardized WR, E, and CO(2), exertional dyspnea and leg effort decreased while inspiratory capacity (IC) increased. Decrease in E was accomplished primarily by decrease in respiratory rate (RR) and increase in both inspiratory time (TI) and expiratory time; VT slightly increased, while inspiratory drive (VT/TI) and duty cycle (TI/total time of the respiratory cycle) remained unchanged. The decrease in Pessw and the increase in VT were associated with lower exertional dyspnea after EXT; (4) at standardized E, VT, RR, and IC, Pessw and Pessw(%Pessn)/VT remained unchanged while exertional dyspnea and leg effort decreased with EXT. CONCLUSION In conclusion, increases in NMC, aerobic capacity, and tolerance to dyspnogenic stimuli and possibly breathing retraining are likely to contribute to the relief of both exertional dyspnea and leg effort after EXT.

Understanding dyspnoea by its language

Dyspnoea is a general term used to characterise a range of qualitatively distinct descriptors that vary in intensity. Based on the hypothesis that various qualities of respiratory discomfort result from different pathophysiological abnormalities, language could help to define one or more of the abnormalities responsible for breathing discomfort. The use of descriptors of dyspnoea may contribute to the understanding of the mechanisms of dyspnoea, and assist in identifying or predicting a specific diagnosis. Symptoms that can be reliably discriminated imply different pathophysiological mechanisms, whereas symptoms that cannot be reliably discriminated imply similar pathophysiological mechanisms. Since dyspnoea is a fundamental part of patients clinical history, physicians should become more fluent in the language of dyspnoea.

Clinical InvestigationsCOPDExercise Training Improves Exertional Dyspnea in Patients With COPDa: Evidence of the Role of Mechanical Factors

BACKGROUND To our knowledge, no data have been reported on the effects of exercise training (EXT) on central respiratory motor output or neuromuscular coupling (NMC) of the ventilatory pump, and their potential association with exertional dyspnea. Accurate assessment of these important clinical outcomes is integral to effective management of breathlessness of patients with COPD. MATERIAL AND METHODS Twenty consecutive patients with stable moderate-to-severe COPD were tested at 6-week intervals at baseline, after a nonintervention control period (pre-EXT), and after EXT. Patients entered an outpatient pulmonary rehabilitation program involving regular exercise on a bicycle. Incremental symptom-limited exercise testing (1-min increments of 10 W) was performed on an electronically braked cycle ergometer. Oxygen uptake (O(2)), carbon dioxide output (CO(2)), minute ventilation (E), time, and volume components of the respiratory cycle and, in six patients, esophageal pressure swings (Pessw), both as actual values and as percentage of maximal (most negative in sign) esophageal pressure during sniff maneuver (Pessn), were measured continuously over the runs. Exertional dyspnea and leg effort were evaluated by administering a Borg scale. RESULTS Measurements at baseline and pre-EXT were similar. Significant increase in exercise capacity was found in response to EXT: (1) peak work rate (WR), O(2), CO(2), E, tidal volume (VT), and heart rate increased, while peak exertional dyspnea and leg effort did not significantly change; (2) exertional dyspnea/O(2) and exertional dyspnea/CO(2) decreased while E/O(2) and E/CO(2) remained unchanged. The slope of both exertional dyspnea and leg effort relative to E fell significantly after EXT; (3) at standardized WR, E, and CO(2), exertional dyspnea and leg effort decreased while inspiratory capacity (IC) increased. Decrease in E was accomplished primarily by decrease in respiratory rate (RR) and increase in both inspiratory time (TI) and expiratory time; VT slightly increased, while inspiratory drive (VT/TI) and duty cycle (TI/total time of the respiratory cycle) remained unchanged. The decrease in Pessw and the increase in VT were associated with lower exertional dyspnea after EXT; (4) at standardized E, VT, RR, and IC, Pessw and Pessw(%Pessn)/VT remained unchanged while exertional dyspnea and leg effort decreased with EXT. CONCLUSION In conclusion, increases in NMC, aerobic capacity, and tolerance to dyspnogenic stimuli and possibly breathing retraining are likely to contribute to the relief of both exertional dyspnea and leg effort after EXT.

Carbon dioxide responsiveness in COPD patients with and without chronic hypercapnia

To ascertain whether and to what extent the reduced ventilatory response to a hypercapnic stimulus in chronic obstructive pulmonary disease (COPD) patients depends on a blunted chemoresponsiveness of central origin or to mechanical impairment, we studied two groups of COPD patients without (group A) and with (group B) chronic hypercapnia, but with similar degrees of airway obstruction and hyperinflation. The study was performed on 17 patients (9 normocapnic and 8 hypercapnic). Six age-matched normal subjects (group C) were also studied as a control. During a CO2 rebreathing test, ventilation (VE), mouth occlusion pressure (P0.1), and the electromyographic activity of diaphragm (Edi) were recorded and then plotted against end-tidal carbon dioxide tension (PCO2). Inspiratory muscle strength was significantly lower in the hypercapnic group (group B) compared to normocapnic group (A), and in these groups compared to the control group (C). Both patient groups exhibited significantly lower delta VE/delta PCO2 than the control group. In hypercapnics, delta P0.1/delta PCO2 was significantly lower than in normocapnics and control group, whilst mouth occlusion pressure as % of maximal inspiratory pressure delta P0.1 (% MIP)/delta PCO2 did not differ significantly among the three groups. delta Edi/delta PCO2 increased from C to A. At a PCO2 of 8.65 kPa, VE was similar in the normocapnic and control group, but lower in hypercapnics; Edi was similar in hypercapnic and control group; but greater in normocapnics. P0.1(% MIP) did not differ significantly among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of dyspnoea and its language in patients with asthma

This study hypothesises that regardless of the global score of dyspnoea intensity, different descriptors may be selected by asthmatic patients during short cardiopulmonary exercise test (sCPET) and methacholine (Mch) inhalation. It also examines whether different qualitative dyspnoea sensations can help explain the underlying mechanisms of the symptom. Minute ventilation (V′E), tidal volume (VT) and inspiratory capacity (IC) were measured in 22 stable asthmatic patients, and the sensation of dyspnoea during Mch inhalation and sCPET was quantitatively (Borg scale) and qualitatively (descriptors) assessed. The work rate and oxygen uptake (V′O2) were also measured during sCPET. Airway obstruction and hyperinflation, as measured by IC reduction, were the best correlates for dyspnoea with Mch. During sCPET, changes in WR, V′O2, V′E and VT significantly correlated with Borg score, with V′E being the best predictor of dyspnoea; IC decreased in eight patients. Furthermore, chest tightness (68%) was the highest reported descriptor during Mch inhalation, whereas work/effort (72%) was the highest during sCPET. In conclusion, obstruction/hyperinflation and work rate are highly reliable predictors of Borg rating of dyspnoea during methacholine inhalation and short cardiopulmonary exercise testing, respectively. Regardless of the global score of intensity dyspnoea, different descriptors may be selected by patients during short cardiopulmonary exercise testing and methacholine inhalation. Various qualities of dyspnoea result from different pathophysiological abnormalities.

Control of breathing in patients with severe hypothyroidism

PURPOSE Hypothyroid patients have been reported to have a blunted ventilatory response to carbon dioxide stimulation. However, previous data did not clarify the localization of abnormalities responsible for that disorder. The present investigation was aimed at evaluating to what extent central (neural) and/or peripheral (muscular) factors are involved in the abnormalities of the ventilatory control system in hypothyroid patients. PATIENTS AND METHODS We studied 13 patients with severe hypothyroidism before and after 6 to 9 months of replacement therapy; 7 age- and sex-matched normal subjects were also studied as a control. In each subject, we assessed (1) inspiratory muscle strength by measuring maximal inspiratory pressure (MIP), and (2) respiratory control system during a carbon dioxide rebreathing test by measuring minute ventilation (VE), tidal volume (VT), mean inspiratory flow (VT/TI), and electromyographic (EMG) activity of the diaphragm (Edi) and intercostal (Eint) muscles. RESULTS Compared with the normal control group (Group C), patients exhibited similar MIP, and similar VE and EMG response slopes to carbon dioxide. However, evaluating individual VE response slopes, we were able to identify two subsets of patients: Group A (six patients) with low VE response (less than mean -SD.1.65 of Group C) and Group B (seven patients) with normal VE response. Compared with both Groups B and C, Group A exhibited significantly lower VT/TI, Edi, and Eint response slopes; the difference between Groups B and C was not significant. Six patients (two from Group A and four from Group B) exhibited low MIP values compared with that in Group C. After replacement therapy, (1) VE, VT/TI, and Edi response slopes increased significantly in Group A; and (2) MIP increased, but not significantly in patients with low MIP. CONCLUSIONS We conclude that: (1) In patients with severe hypothyroidism, the ventilatory control system may be altered at the neural level, as indicated by a blunted chemosensitivity; (2) Impaired respiratory muscle function does not seem to play a major role in the decreased ventilatory response to carbon dioxide stimulation; (3) Replacement therapy appears to normalize the response to hypercapnic stimulation, but not respiratory muscle strength.

Chest wall kinematics and respiratory muscle action in ankylosing spondylitis patients

No direct measurements of the pressures produced by the ribcage muscles, the diaphragm and the abdominal muscles during hyperventilation have been reported in patients with ankylosing spondylitis. Based on recent evidence indicating that abdominal muscles are important contributors to stimulation of ventilation, it was hypothesised that, in ankylosing spondylitis patients with limited ribcage expansion, a respiratory centre strategy to help the diaphragm function may involve coordinated action of this muscle with abdominal muscles. In order to validate this hypothesis, the chest wall response to a hypercapnic/hyperoxic rebreathing test was assessed in six ankylosing spondylitis patients and seven controls by combined analysis of: 1) chest wall kinematics, using optoelectronic plethysmography, this system is accurate in partitioning chest wall expansion into the contributions of the ribcage and the abdomen; and 2) respiratory muscle pressures, oesophageal, gastric and transdiaphragmatic (Pdi); the pressure/volume relaxation characteristics of both the ribcage and the abdomen allowed assessment of the peak pressure of both inspiratory and expiratory ribcage muscles, and of the abdominal muscles. During rebreathing, chest wall expansion increased to a similar extent in patients to that in controls; however, the abdominal component increased more and the ribcage component less in patients. Peak inspiratory ribcage, but not abdominal, muscle pressure was significantly lower in patients than in controls. End-inspiratory Pdi increased similarly in both groups, whereas inspiratory swings in Pdi increased significantly only in patients. No pressure or volume signals correlated with disease severity. The diaphragm and abdominal muscles help to expand the chest wall in ankylosing spondylitis patients, regardless of the severity of their disease. This finding supports the starting hypothesis that a coordinated response of respiratory muscle activity optimises the efficiency of the thoracoabdominal compartment in conditions of limited ribcage expansion.