Roberto Duranti

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.

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.

Breathing pattern and kinematics in normal subjects during speech, singing and loud whispering

Aims:  We used for the first time a non‐invasive optoelectronic plethysmography to assess breathing movements and to provide a quantitative description of chest wall kinematics during phonation.

Control of breathing in patients with limb girdle dystrophy : a controlled study

BACKGROUND--In patients with limb girdle dystrophy the relative contribution of peripheral factors (respiratory muscle weakness, and lung and/or airway involvement) and central factors (blunted and/or inadequate chemoresponsiveness) in respiratory insufficiency has not yet been established. To resolve this, lung volumes, arterial blood gas tensions, respiratory muscle strength, breathing pattern and neural respiratory drive were investigated in a group of 15 patients with limb girdle dystrophy. An age-matched normal group was studied as a control. METHODS--Respiratory muscle strength was assessed as an arithmetic mean of maximal inspiratory (MIP) and expiratory (MEP) pressures. Breathing pattern was evaluated in terms of volume (ventilation VE, tidal volume VT) and time (respiratory frequency Rf, inspiratory time TI, expiratory time TE) components of the respiratory cycle. Neural respiratory drive was assessed as the mean inspiratory flow (VT/TI), mouth occlusion pressure (P0.1) and electromyographic activity (EMG) of the diaphragm (EMGd) and the intercostal parasternal (EMGp) muscles. In 10 of the 15 patients the responses to carbon dioxide (PCO2) stimulation were also evaluated. RESULTS--Most patients exhibited a moderate decrease in vital capacity (VC) (range 37-87% of predicted), MIP (range 23-84% of predicted), and/or MEP (range 13-41% of predicted). The arterial carbon dioxide tension (PaCO2) was increased in three patients breathing room air, while PaO2 was normal in all. Compared with the control group Rf was higher, and VT, TI and TE were lower in the patients. EMGd and EMGp were higher whilst VT/TI and P0.1 were normal in the patients. Respiratory muscle strength was inversely related to EMGd and EMGp. PaCO2 was found to relate primarily to VC and duration of illness, but not to respiratory muscle strength. During hypercapnic rebreathing delta VE/delta PCO2, delta VT/delta PCO2, and delta P0.1/delta PCO2 were lower than normal, whilst delta EMGd/delta PCO2 and delta EMGp/delta PCO2 were normal in most patients. A direct relation between respiratory muscle strength and delta VT/delta PCO2 was found. CONCLUSIONS--The respiratory muscles, especially expiratory ones, are weak in patients with limb girdle dystrophy. Reductions in respiratory muscle strength are associated with increased neural drive and decreased ventilatory output (delta VT/delta PCO2). The decrease in VC, together with the duration of disease, influence PaCO2. VC is a more useful test than respiratory muscle strength for following the course of limb girdle dystrophy.

Desensitization of the cough reflex by exercise and voluntary isocapnic hyperpnea

Little is known about the effects of exercise on the sensory and cognitive aspects of coughing evoked by inhalation of tussigenic agents. The threshold for the cough reflex induced by inhalation of increasing nebulizer outputs of ultrasonically nebulized distilled water (fog), an index of cough reflex sensitivity, was assessed in twelve healthy humans in control conditions, during exercise and during voluntary isocapnic hyperpnea (VIH) at the same ventilatory level as the exercise. The intensity of the urge to cough (UTC), a cognitive component of coughing, was recorded throughout the trials on a linear scale. The relationships between inhaled fog nebulizer outputs and the correspondingly evoked UTC values, an index of the perceptual magnitude of the UTC sensitivity, were also calculated. Cough appearance was always assessed audiovisually. At an exercise level of 80% of anaerobic threshold, the median cough threshold was increased from a control value of 0.73 to 2.22 ml/min (P<0.01), i.e., cough sensitivity was downregulated. With VIH, the threshold increased from 0.73 to 2.22 ml/min (P<0.01), a similar downregulation. With exercise and VIH compared with control, mean UTC values at cough threshold were unchanged, i.e., control, 3.83 cm; exercise, 3.12 cm; VIH, 4.08 cm. The relationship of the fog nebulizer output/UTC value was linear in control conditions and logarithmic during both exercise and VIH. The perception of the magnitude of the UTC seems to be influenced by signals or sensations arising from exercising limb and thoracic muscles and/or by higher nervous (cortical) mechanisms. The results indicate that the adjustments brought into action by exercise-induced or voluntary hyperpnea exert inhibitory influences on the sensory and cognitive components of fog-induced cough.

Mechanical loading and control of breathing in patients with severe chronic obstructive pulmonary disease.

BACKGROUND--High neural drive to the respiratory muscles and rapid and shallow breathing are frequently observed in patients with chronic obstructive pulmonary disease (COPD), and both mechanical and chemical factors are thought to play a part. However, the interrelation between these factors and the modifications in the control of breathing are not clearly defined. The effects of an acute decrease in mechanical load by the administration of a high dose of a beta 2 agonist were studied. METHODS--Nine spontaneously breathing patients with severe COPD took part in the study. Criteria for entry were FEV1 of < 40% of predicted and an improvement in FEV1 of < 200 ml after inhalation of 400 micrograms fenoterol. The following parameters were measured: lung volumes, tidal volume (VT), respiratory frequency (Rf), maximal pleural pressure during a sniff manoeuvre (PPLmax), pleural pressure swings (PPLsw), lung resistance (RL), RL/PPLmax ratio, and surface electromyographic activity (EMG) of diaphragm (EDI) and parasternal (EPS) muscles. Arterial oxygen saturation (SaO2), end tidal carbon dioxide pressure (PETCO2), and the electrocardiogram were also monitored. Each variable was measured under control conditions and 20 and 40 minutes after the inhalation of 800 micrograms fenoterol. In five patients the effects of placebo were also studied. RESULTS--Fenoterol resulted in an increase in FEV1 and decrease in FRC. SaO2 did not change, while PETCO2 fell and heart rate increased. The VT increased, and Rf decreased, PPLsw fell and PPLmax increased, thus the PPLsw/PPLmax ratio fell. Both RL and RL/PPLmax also fell, and a substantial decrease in EDI and EPS was observed. Changes in PPLsw were related to changes in FEV1 and RL. Changes in VT and Rf, and EDI/TI and EPS/TI were also related to changes in PPLsw and RL/PPLmax ratio, but not to changes in FEV1. No variation was observed with placebo. CONCLUSIONS--In patients with severe COPD a decrease in inspiratory muscle loading relative to the maximal available strength, as expressed by the RL/PPLmax and PPLsw/PPLmax ratios, appears to be the major determinant of changes in breathing pattern and inspiratory muscle activity (decrease in EMG).