Breathing pattern and chest wall kinematics during phonation in chronic obstructive pulmonary disease patients.

BACKGROUND: Breathing pattern description and chest wall kinematics during phonation have not been studied in male and female patients with chronic obstructive pulmonary disease. OBJECTIVES: We used optoelectronic plethysmography to provide a quantitative description of breathing pattern and chest wall kinematics. METHODS: Volumes of chest wall compartments (rib cage and abdomen) were assessed in 15 patients while reading aloud (R), singing (SI) and during high-effort whispering (HW). RESULTS: Relative to quiet breathing, tidal volume and expiratory time increased while inspiratory time decreased. The expiratory flow decreased during R and SI, but was unchanged during HW. In males, the end-expiratory volume decreased as a result of a decreased volume of rib cage during R, SI and HW and due to a decreased volume of abdomen during HW. In females, a decrease in end-expiratory volume was accomplished by a decrease in abdominal volume during R and HW. During R, the chest wall end-expiratory volume of the last expiration in females was to the left of the maximal expiratory flow volume curve (MEFV), with still substantial expiratory reserve volume available. In contrast, during SI and HW in females and during all types of phonation in males, chest wall end-expiratory volume of the last expiration was well to the right of the MEFV curve and associated with respiratory discomfort. Gender had a greater importance than physical characteristics in determining more costal breathing in females than in males under all conditions studied. CONCLUSIONS: Phonation imposes more abdominal breathing pattern changes in males and costal changes in females. Expiratory flow encroaches upon the MEFV curve with higher phonatory efforts and respiratory discomfort.

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.

Suppression of ventilatory muscle activity in healthy subjects and COPD patients with negative pressure ventilation.

We evaluated the ability of NPV to suppress EMGd and EMGint in seven patients with severe COPD and five normal subjects. Subjects were studied either without (A) or with mouthpiece and nose clip (B). Electromyographic suppression was assessed comparing EMG activity during NPV with the control activity without a mouthpiece and prior to the initiation of the NPV run. In normal subjects, in A, NPV resulted in a partial suppression of EMGd; in B, prior to NPV, EMGd rose compared with A prior to NPV. In patients, in A, NPV resulted in a suppression of both EMGd and EMGint. In B, prior to NPV, both EMGd and EMGint rose compared with A prior to NPV. Thus, it seems that NPV is able to produce a consistent reduction in inspiratory muscle EMG activity. This variable NPV ability would have to be assessed for better selection criteria for patient candidates in a rehabilitation program.

Preventive effects of beclomethasone on histamine-induced changes in breathing pattern in asthma.

Bronchial mucosa inflammation is a hallmark of asthma. Epithelial damage due to inflammatory process may contribute to induce a pattern of rapid and shallow breathing (RSB). Probably due to its effects on inflammatory process, beclomethasone dipropionate (BDP) decreases bronchial hypersensitivity (BH), as assessed in terms of histamine concentration causing a 20 percent FEV1 decrease from saline solution (PC20FEV1); however, no data are available on the effect of BDP on RSB. We studied 32 asymptomatic asthmatic subjects with a severe to moderate levels of BH (PC20FEV1 0.01 to 1.7 mg/ml). After they were randomly assigned to one month of either BDP (2 mg daily, 17 patients) or placebo (15 patients), they inhaled progressively doubling concentrations of histamine phosphate by tidal breathing method. With histamine in seven BDP-treated and in five placebo-treated patients, decrease in FEV1 > or = 20 percent from saline solution was paralleled by a significant decrease in tidal volume (VT), inspiratory time (Ti), and expiratory time (Te), and increase in respiratory frequency (RF). In the remaining patients, histamine failed to change the breathing pattern. In the seven RSB patients, BDP resulted in a smaller VT decrease (p < 0.02) and a smaller RF increase (p < 0.02) with histamine. The five RSB placebo-treated patients were then given one month BDP (2 mg daily): inhaled BDP, but not placebo, resulted both in a significant increase in PC20FEV1 and modulation in histamine-induced changes in breathing pattern. We conclude that high doses of BDP seem to be able to modulate histamine-induced RSB, an effect that might be linked to reversal of airway inflammation.

Hypoxic and hypercapnic breathlessness in patients with type I diabetes mellitus.

STUDY OBJECTIVES: The putative role of the performance of inspiratory muscles and breathing pattern in inducing dyspnea has been recently assessed during hypoxic stimulation in patients with type I diabetes (IDDM). Compared to a hypoxic stimulus, a hypercapnic stimulus, which may differently affect the pattern of breathing, could therefore modulate the coupling between respiratory effort and ventilatory output, which is involved in dyspnea sensation. SUBJECTS: Eight stable patients aged 19 to 48 years old, with IDDM (duration of disease, 36 to 240 months) and no smoking history, cardiopulmonary involvement, or autonomic neuropathy; and an age- and sex-matched control group. MEASUREMENTS: Pulmonary volumes, diffusing capacity of the lung for carbon monoxide, time and volume components (tidal volume [VT] and respiratory frequency), dynamic elastance (Eldyn), and swings in pleural pressure (Pessw) were measured. Maximal inspiratory pleural pressure (Pes) during a maximal sniff maneuver (Pessn), respiratory muscle effort or output (Pessw%Pessn), tension time index (TTI) = TI/total breathing cycle time x Pessw(%Pessn), and swing in Pes during VT as a percentage of Pessn were also evaluated. Dyspnea sensation was assessed by a modified Borg scale. Subjects were studied at baseline and during hypoxic and hypercapnic rebreathing tests. RESULTS: Compared to control subjects, patients exhibited normal routine spirometric function and Pessn, but a higher Eldyn, indicating peripheral airway involvement. In patients, but not in control subjects, Eldyn increased during both chemical stimuli and increased more during hypoxia than during hypercapnia. Also, changes in both VT and Pessw(%Pessn) on changes in PCO(2) were lower, while changes in Pessw(%Pessn)/VT, an index of neuroventilatory dissociation (NVD) of the ventilatory pump, on changes in PCO(2) were greater. Changes in VT and NVD for unit change in arterial oxygen saturation were lower and higher, respectively. Changes in Borg scale per changes in NVD were greater during both stimuli. Furthermore, compared to hypoxic conditions, a greater VT for any level of both minute volume and Pessw(%Pessn), and lower changes in Borg scale on changes in Pessw(%Pessn) and Pessw(%Pessn)/VT were found in hypercapnia. Changes in NVD and Borg scale related to changes in Eldyn with both chemical stimuli. CONCLUSIONS: In IDDM, the greater perception of dyspnea is associated with changes in inspiratory effort being out of proportion to changes in VT. The greater increase in Eldyn and the lower increase in VT may, in part, account for the greater perception of breathlessness during hypoxia.

Control of breathing in a subset of patients with systemic lupus erythematosus.

BACKGROUND: Inspiratory muscle weakness and abnormalities in breathing pattern and in respiratory drive have been reported in patients with multisystem disorders. In patients with systemic lupus erythematosus (SLE), data on respiratory muscle strength and control of breathing are scarce. METHODS: We studied a subset of nine female patients with SLE with no major findings of cardiovascular, renal, or neurologic involvement, and with a normal routine chest radiograph. An age- and sex-matched normal group was also studied as a control. We evaluated lung volumes, diffusing lung properties (TLCO, TLCO/VA), maximal inspiratory (MIP) and expiratory (MEP) pressures, end-tidal carbon dioxide tension (PCO2), and breathing pattern: ventilation (VE), tidal volume (VT), inspiratory time (TI), and respiratory frequency (Rf). Neural respiratory drive, assessed in terms of mean inspiratory flow (VT/TI), mouth occlusion pressure (P0.1), and surface electromyographic activity of the diaphragm (Edi) and intercostal (Eps) muscles was also evaluated. RESULTS: As a whole, patients exhibited mild decrease in MIP; vital capacity was slightly reduced in two patients and TLCO/VA was moderately reduced in three. During a hypercapnic rebreathing test, delta VT/delta PCO2 was lower, delta P0.1/delta PCO2 was normal, while delta Edi/delta PCO2 and delta Eps/delta PCO2 were higher in patients compared with normal control subjects. delta VT/delta PCO2 significantly related to MIP. At 60 mm Hg of PCO2 patients maintained the rapid and shallow pattern of breathing (RSB) exhibited during room-air breathing: lower VT, shorter TI, and greater Rf, with VE, VT/TI, and Edi being greater compared with the normal control subjects. CONCLUSIONS: These data seem to indicate that in this SLE subset, mild decrease in respiratory muscle strength may accompany an increased respiratory drive, and contribute to a qualitatively abnormal ventilatory response (RSB) to carbon dioxide stimulation.

Four-week negative pressure ventilation improves respiratory function in severe hypercapnic COPD patients.

Studies on respiratory muscle resting by negative pressure ventilation (NPV) in patients with stable COPD have given conflicting results. Probable explanations lie in criteria of patients' selection, method of NPV application, and lack of supervision of respiratory muscle rest. Thirteen hypercapnic patients with COPD were, therefore, randomly assigned to either a NPV group or a control group. The NPV was applied by an airtight jacket (pneumosuit), 5 h a day, 5 consecutive days a week for 4 weeks. Both NPV group and control group performed in-hospital pulmonary rehabilitation program for a 4-week period. Arterial blood gases, spirometry, maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP), breathing pattern, and electromyogram (EMG) of the diaphragm and parasternal intercostal muscles were measured on the preintervention day, and at the end of the second and fourth weeks of treatment (days 13 and 27, respectively). The short-term effect of NPV on EMG suppression was also checked throughout the ventilatory sessions in three different days (1, 12, and 26, respectively). A 6-min walking test (WT) and level of dyspnea by a modified Borg scale were evaluated on the preintervention and the last days. Negative pressure ventilation resulted in a significant reduction in EMG activity of both diaphragm and parasternal muscles, associated with significant increase in MIP, tidal volume, and ventilation, and increase in PaO2 and decrease in PaCO2. A significant relationship between change in MIP and change in PaCO2 was observed (r = 0.72, p < 0.01). Improve-ment in 6-min WT and dyspnea sensation was also observed, both being the sole changes in the control group. These data seem to indicate a beneficial role of respiratory muscle rest in improving respiratory function. Adequate supervision by personnel familiar with the equipment is likely to contribute to successful treatment.

Perception of dyspnea in patients with neuromuscular disease.

BACKGROUND: The perception of dyspnea is not a prominent complaint of resting patients with neuromuscular disease (NMD). To our knowledge, no study has been addressed at evaluating the interrelationships among lung mechanics, respiratory motor output, and the perception of dyspnea in patients with NMD receiving ventilatory stimulation. MATERIAL: Eleven patients with NMD (mean +/- SD age, 44 +/- 11.8 years; 5 men) of different etiology and a group of normal subjects matched for age and sex (control subjects). METHODS: While patients were breathing room air, lung volumes, arterial blood gases, the pattern of breathing (minute ventilation [E], tidal volume [VT], respiratory frequency, inspiratory time), and maximal (less negative) esophageal pressure during a sniff maneuver (Pessn), as an index of inspiratory muscle strength, were measured. Then we evaluated the response to hypercapnic-hyperoxic stimulation (hypercapnic-hyperoxic rebreathing test [RT]) in terms of breathing pattern, inspiratory swing of pleural pressure (Pessw), and inspiratory effort (Pessw[%Pessn]). During the RT, dyspnea was assessed every 30 s using a modified Borg scale (0 to 10). RESULTS: Pulmonary volumes were reduced in seven patients, and PCO(2) was out of proportion to E in four patients. Group Pessn was 42.8 +/- 23.6 cm H(2)O in patients and 107 +/- 20.4 cm H(2)O in control subjects (p < 0.001). Dynamic elastance (Eldyn) [p = 0.0016] and Pessw(%Pessn) [p < 0.0005] were higher in patients. During the RT, Borg/CO(2), Pessw(%Pessn)/CO(2), and Borg/Pessw(%Pessn) were similar in the two groups, while E/CO(2) and VT/CO(2) were lower in patients (p < 0.0002 for both). As a consequence, for unit change in VT (percentage of predicted vital capacity [%VC]), greater changes in Pessw(%Pessn) were associated with greater Borg scores in patients. Baseline Eldyn related to Pessw(%Pessn)/VT(%VC) during hypercapnia (r(2) = 0.85), an index of neuroventilatory coupling of the ventilatory pump (NVC). NVC predicted a good amount of the variability in Borg/E (r(2) = 0.46, p < 0.02). CONCLUSIONS: In this subset of NMD patients during hypercapnic stimulation, a normal inspiratory motor output per unit change in PCO(2) results in a shallow breathing pattern. The consequent impairment of NVC underlies the higher scoring of dyspnea in these patients.

Do inhaled corticosteroids affect perception of dyspnea during bronchoconstriction in asthma?

BACKGROUND: Some of the disagreements on the perception of dyspnea (PD) during bronchoconstriction in asthma patients could depend on the interrelationships among the following: (1) the influence of baseline airflow obstruction on the patient's ability to detect any further increase in airway resistance; (2) the effect of eosinophilic inflammation on the airway; (3) bronchial hyperresponsiveness (BHR); and (4) the effect of inhaled corticosteroids (ICSs). OBJECTIVE: We hypothesized that if the inflammation of the airway wall influences to some extent and in some way the PD in asthma patients, ICSs reverse the effect of airway inflammation on the PD. METHODS: We studied 100 asthma patients who were divided into the following four groups: patients with obstruction who were either ICS-naive (group I) or were treated with ICSs (group II); and nonobstructed patients who were either ICS-naive (group III) or were treated with ICSs (group IV). PD on the visual analog scale (VAS) was assessed during a methacholine-induced FEV(1) decrease and specifically was quantified as the VAS slope and score at an FEV(1) decrease of 5 to 20%. BHR was assessed in terms of the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)). Eosinophil counts in induced sputum samples also were performed. Regression analysis, univariate analysis of variance, and factor analysis were applied for statistical evaluation. RESULTS: For a 5 to 20% fall in FEV(1) from the lowest point after saline solution induction, VAS score was lowest in group II, slightly higher in group I, slightly higher still in group IV, and the highest in group III. In the patients as a whole, BHR related to PD, but age, clinical score, duration of the disease, and presence of baseline airway obstruction did not. In patients with obstruction who were treated with ICSs, eosinophil counts related to PD negatively. Factor analysis yielded the following four factors that accounted for 70% of the variance in the data: ICS; eosinophil counts; FEV(1); and PC(20) loaded on separated factors with PD loading on the same factors as PC(20). The post hoc analysis carried out dividing the patients into ICS-treated and ICS-naive, showed that in the former group eosinophil counts and BHR proved to be factors negatively associated with PD, while in the latter group eosinophil counts were positively associated with PD. CONCLUSIONS: We have shown that eosinophilic inflammation of the airway wall may increase PD and that the association of eosinophil counts with ICSs may result in lessening the PD.

Respiratory muscle function and hypoxic ventilatory control in patients with type I diabetes.

STUDY OBJECTIVES: The interaction among pulmonary mechanics, respiratory muscle performance, and ventilatory control in subjects with insulin-dependent diabetes mellitus has so far received little attention. We therefore decided to assess the role of central factors and peripheral factors on the ventilatory response to a hypoxic stimulus in type I diabetic patients. SUBJECTS: Eight patients in stable condition aged 19 to 48 years old, with insulin-dependent diabetes mellitus (duration of the disease, 36 to 240 months) and no history of smoking, cardiopulmonary involvement, or autonomic neuropathy; and an age- and gender-matched control group. MEASUREMENTS: In each patient, we measured the following: pulmonary volumes; diffusing capacity of the lung for carbon monoxide (D(LCO)); time and volume components of ventilation (tidal volume [V(T)] and respiratory frequency); static compliance (Clstat) and dynamic compliance (Cldyn); swings in pleural pressure (Pes) and gastric pressure (Pg); and transdiaphragmatic pressure (Pdi), obtained by subtracting Pes from Pg. Maximal inspiratory Pes and Pdi during a maximal sniff maneuver were also measured. Swings in Pes and Pdi during V(T) as a percentage of Pes and Pdi during the maximal sniff maneuver [Pessw(%Pessn) and Pdisw(%Pdisn), respectively] were both considered as a measure of central respiratory output, and the Pessw(%Pessn)/V(T) ratio was considered as an index of neuroventilatory dissociation (NVD) of the inspiratory pump. Subjects were studied at baseline and during hypoxic rebreathing. RESULTS: Pulmonary volumes and D(LCO) were normal or slightly reduced. A lower Cldyn, higher central respiratory output, and NVD were found. During hypoxic rebreathing, patients had lower V(T), similar central respiratory output, and greater NVD per unit change in arterial oxygen saturation compared with values in control subjects. An increase in dynamic elastance, computed as 1/Cldyn, during hypoxia was found in patients, but not in normal subjects, and was directly related to concurrent changes in NVD. CONCLUSIONS: We have shown that the assessment of a normal Clstat and normal routine parameters of airway obstruction does not permit the definite exclusion of the role of peripheral airway involvement in insulin-dependent diabetes mellitus. Peripheral airway involvement is likely to influence indices of hypoxic ventilator) drive by modulating a normal central motor output into a rapid and shallow pattern of ventilatory response.

Mechanism of CO(2) retention in patients with neuromuscular disease.

BACKGROUND: In many studies of patients with muscle weakness, chronic hypercapnia has appeared to be out of proportion to the severity of muscle disease, indicating that factors other than muscle weakness are involved in CO(2) retention. In patients with COPD, the unbalanced inspiratory muscle loading-to-strength ratio is thought to trigger the signal for the integrated response that leads to rapid and shallow breathing and eventually to chronic hypercapnia. This mechanism, although postulated, has not yet been assessed in patients with muscular dystrophy. SUBJECTS: Twenty consecutive patients (mean age, 47.6 years; range, 23 to 67 years) were studied: 11 patients with limb-girdle dystrophy, 3 with Duchenne muscular dystrophy, 1 with Charcot-Marie-Tooth syndrome, 1 with Becker muscular dystrophy, 1 with myotonic dystrophy, 1 with facioscapulohumeral dystrophy, and 2 with amyotrophic lateral sclerosis, without any respiratory complaints. Seventeen normal subjects matched for age and sex were studied as a control group. METHODS: Routine spirometry and arterial blood gases, maximal inspiratory and expiratory muscle pressures (MIP and MEP, respectively), and pleural pressure during maximal sniff test (Pplsn), were measured. Mechanical characteristics of the lung were assessed by evaluating lung resistance (RL) and dynamic elastance (Eldyn). Eldyn was assessed as absolute value and as percent of Pplsn; Eldyn (%Pplsn) indicates the elastic load per unit of inspiratory muscle force. Breathing pattern was assessed in terms of time (inspiratory time [TI]; respiratory frequency [Rf]) and volume (tidal volume [VT]) components of the respiratory cycle. RESULTS: A rapid shallow breathing pattern, as indicated by a greater Rf/VT ratio and a lower TI, was found in study patients compared to control subjects. Eldyn was greater in study patients, while MIP, MEP, and Pplsn were lower. PaCO(2) inversely related to VT, TI, and Pplsn (p = 0.012, p = 0.019, and p = 0.002, respectively), whereas it was directly related to Rf, Rf/VT, Eldyn, and Eldyn (%Pplsn) (p < 0.004 to p < 0.0001). Also Eldyn (%Pplsn) inversely related to TI, and the latter positively related to VT. In other words, increase in Eldyn (%Pplsn) was associated with decrease in TI, and the latter was associated with lower VT and greater PaCO(2). Mechanical and breathing pattern variables were introduced in a stepwise multiple regression that selected Eldyn (%Pplsn) (p < 0.0001; r(2) = 0.62) as a unique independent predictor of PaCO(2). CONCLUSIONS: The present study shows that in patients with neuromuscular disease, elastic load and respiratory muscle weakness are responsible for a rapid and shallow breathing pattern leading to chronic CO(2) retention.

Assessing inspiratory muscle strength in patients with neurologic and neuromuscular diseases : comparative evaluation of two noninvasive techniques.

STUDY OBJECTIVES: Static mouth pressure during maximal inspiratory efforts is commonly used to evaluate inspiratory muscle strength. However, maximal inspiratory pressure (MIP) presents some potential limitations likely to be overcome by the measure of mouth pressure during a maximal sniff maneuver in patients with respiratory muscle weakness. The aim of the present study was to assess whether mouth pressure during sniff maneuver (Pmosn) is a better index of inspiratory muscle strength than MIP in patients with neurologic and neuromuscular diseases (NNMD) with and without inspiratory muscle weakness. SUBJECTS AND MEASUREMENTS: Both MIP and Pmosn were measured in 30 patients affected by various types of NNMD and in 41 control subjects. Pmosn was measured with a 5-cm latex balloon-catheter system, the balloon being held in the oral cavity with the lips closed. RESULTS: In control subjects, MIP was either similar (in female subjects) or higher (in male subjects) than Pmosn, the variation coefficients for the two tests being similar both in male subjects (19.3% vs 19.1% for MIP and Pmosn, respectively) and in female subjects (27.5% vs 26.2%, respectively). There was no difference in the Pmosn/MIP ratios observed in the different diseases (one-way analysis of variance, F = 0.29, p = 0.91). In control subjects, a significant inverse relationship between Pmosn/MIP ratio and MIP (r = - 0.66, p < 0.00001) was found, ie, the lower the MIP, the higher the Pmosn/MIP ratio, suggesting an increasing difficulty in performing MIP as MIP values decreased. The majority of patients were between the prediction limits of the regression calculated for control subjects. At variance, patients with Duchenne dystrophy and low MIP were under the prediction limits of the regression calculated for control subjects, indicating a lower-than-expected PMOSN. CONCLUSIONS: In patients with NNMD, irrespective of the etiology, we found the following: (1) Pmosn does not overcome the limitations of MIP measurement; (2) the two maneuvers are not interchangeable, but rather complement one another in the assessment of inspiratory muscle strength; (3) Pmosn may underestimate muscle strength as assessed by MIP in patients with NNMD with inspiratory muscle weakness; and (4) in patients with low MIP, the lower-than-expected Pmosn/MIP ratio confirms inspiratory muscle weakness.

Changes in ventilatory muscle function with negative pressure ventilation in patients with severe COPD.

Patients with severe COPD may be in a state of ventilatory muscle (VM) fatigue. In these patients, rapid and shallow breathing has been hypothesized to be a compensatory mechanism that prevents more severe fatigue from taking place. To test these hypotheses, we studied the effects of VM resting in a group of patients with severe COPD. Eleven clinically stable patients with COPD and chronic hypercapnia were studied. Six of them (group A) had a seven-day period of negative pressure-assisted ventilation (NPV), and five (group B) with similar functional characteristics served as a control group. Compared with a normal age-matched control group, both A and B groups exhibited significantly lower tidal volume (VT), inspiratory time (TI), total time of the respiratory cycle (Ttot) and Ti/Ttot ratio, decrease in muscle strength, and greater electromyographic activity of diaphragm (EMGd) and parasternal muscles, but similar ventilation and VT/TI. After the study period, group A exhibited significant increase in VT, Ti, and TI/Ttot (p less than 0.05), and decrease in PaCO2 (p less than 0.05), EMGd, and EMGint (p less than 0.05 for both), and a slight but significant increase in maximal inspiratory pressure (MIP) (p less than 0.05). These data suggest that NPV rests VM, increases their strength, and reduces hypercapnia in patients with severe COPD.

Neural respiratory drive and neuromuscular coupling in patients with chronic obstructive pulmonary disease (COPD).

In 15 spontaneously breathing patients with chronic obstructive pulmonary disease (COPD) divided into two groups, one with normocapnia (A) and one with chronic hypercapnia (B), we evaluated the maximal voluntary inspiratory muscle strength (MIP), the pattern of breathing, the mouth occlusion pressure (Po.1), the neural respiratory drive (NRD), assessed by surface electromyographic (EMG) activity of the diaphragm (EMGd) and EMG activity of intercostal muscles (EMGint), and the chest wall neuromuscular coupling, assessed in terms of Po.1/EMGd ratio. Compared with an age-matched normal control group, both A and B groups exhibited lower MIP, significantly greater EMGd and EMGint, and lower Po.1/EMGd ratio. However, a similar pattern, along with a rapid and shallow breathing, differentiated group B from group A. In group B we found a significant direct relationship between Po.1/EMGd ratio and MIP, and an inverse relationship between PaCO2 and Po.1/EMGd ratio. These data seem to indicate the following: (1) EMG is a more precise method than Po.1 in assessing the magnitude of the NRD; (2) NRD is increased in these patients; and (3) clinical manifestations probably associated with inspiratory muscle fatigue (marked decrease in muscle strength, rapid and shallow breathing, and alveolar hypoventilation) may be accompanied by a greater NRD and a more marked derangement in chest wall neuromuscular coupling in COPD.

Neural respiratory drive and neuromuscular coupling during CO2 rebreathing in patients with chronic interstitial lung disease.

In 12 patients with CILD and 18 age-matched normal subjects we assessed the ventilatory control system at three levels: (a) neural, as assessed by EMGd (XP/Ti) and EMGint muscles via surface electrodes; (b) muscular, as assessed by mouth occlusion pressure (P0.1); and (c) ventilatory, as assessed by both ventilation (VE) and the related parameters, tidal volume (VT) and respiratory frequency (f). Compared with a normal control group, patients exhibited a significant decrease in lung volumes and in MIP; VT and inspiratory time (Ti) were significantly lower, while VT/Ti, P0.1, and both EMGd and EMGint were significantly greater in patients. During a CO2 rebreathing test, patients exhibited significantly greater EMGd, EMGint, and P0.1 responses to increasing PETCO2 than the control group. VE response slopes were similar in the two groups. For a given EMGd response slope (delta XP/Ti/delta PETCO2), the average P0.1 response slope (delta P0.1/delta PETCO2) was found to be significantly lower in patients than in the normal control group. Compared with normal subjects, CILD patients have a normal or increased neural component of respiratory activity and relatively low neuromuscular coupling (delta P0.1/delta XP/Ti). The decreased neuromuscular coupling could be explained in these patients by a reduced inspiratory muscle strength.

Respiratory responses induced by the activation of somatic nociceptive afferents in humans.

To further investigate the role of somatic nociceptive afferents in the neural control of breathing, we studied the respiratory effects of their activation by means of either electrical stimulation or ischemic pain in 14 healthy volunteers. Painful electrical cutaneous stimulation increased respiratory frequency (f), mean inspiratory flow (VT/TI), and rate of rise (XP/TI) of integrated electromyographic activity of diaphragm (IEMGdi). Painful muscular electrical stimulation caused similar but larger changes accompanied by increases in tidal volume (VT), peak XP of IEMGdi, and ventilation (VE); it also entrained respiratory rhythm. Ischemic pain, which was characterized by a progressively increasing intensity, caused augmentation in respiratory activity that displayed an increasing trend: VE, f, VT, XP, VT/TI, and XP/TI increased. In the light of available literature, it seems conceivable to suggest that respiratory responses to painful electrical stimulation are mediated through the activation of cutaneous (A delta) and muscular (group III) fine-myelinated afferents, and responses to ischemic pain are mediated by the activation of both fine myelinated (group III) and unmyelinated (group IV) muscular afferents. The input conveyed by these afferents may constitute an effective stimulus to respiration in humans.

Chest wall kinematics and respiratory muscle action in walking healthy humans.

We studied chest wall kinematics and respiratory muscle action in five untrained healthy men walking on a motor-driven treadmill at 2 and 4 miles/h with constant grade (0%). The chest wall volume (Vcw), assessed by using the ELITE system, was modeled as the sum of the volumes of the lung-apposed rib cage (Vrc,p), diaphragm-apposed rib cage (Vrc,a), and abdomen (Vab). Esophageal and gastric pressures were measured simultaneously. Velocity of shortening (V(di)) and power [Wdi = diaphragm pressure (Pdi) x V(di)] of the diaphragm were also calculated. During walking, the progressive increase in end-inspiratory Vcw (P < 0.05) resulted from an increase in end-inspiratory Vrc,p and Vrc,a (P < 0.01). The progressive decrease (P < 0.05) in end-expiratory Vcw was entirely due to the decrease in end-expiratory Vab (P < 0.01). The increase in Vrc,a was proportionally slightly greater than the increase in Vrc,p, consistent with minimal rib cage distortion (2.5 +/- 0.2% at 4 miles/h). The Vcw end-inspiratory increase and end-expiratory decrease were accounted for by inspiratory rib cage (RCM,i) and abdominal (ABM) muscle action, respectively. The pressure developed by RCM,i and ABM and Pdi progressively increased (P < 0.05) from rest to the highest workload. The increase in V(di), more than the increase in the change in Pdi, accounted for the increase in Wdi. In conclusion, we found that, in walking healthy humans, the increase in ventilatory demand was met by the recruitment of the inspiratory and expiratory reserve volume. ABM action accounted for the expiratory reserve volume recruitment. We have also shown that the diaphragm acts mainly as a flow generator. The rib cage distortion, although measurable, is minimized by the coordinated action of respiratory muscles.

Rib cage mechanics during quiet breathing and exercise in humans.

During exercise, large pleural, abdominal, and transdiaphragmatic pressure swings might produce substantial rib cage (RC) distortions. We used a three-compartment chest wall model (J. Appl. Physiol. 72: 1338-1347, 1992) to measure distortions of lung- and diaphragm-apposed RC compartments (RCp and RCa) along with pleural and abdominal pressures in five normal men. RCp and RCa volumes were calculated from three-dimensional locations of 86 markers on the chest wall, and the undistorted (relaxation) RC configuration was measured. Compliances of RCp and RCa measured during phrenic stimulation against a closed airway were 20 and 0%, respectively, of their values during relaxation. There was marked RC distortion. Thus nonuniform distribution of pressures distorts the RC and markedly stiffens it. However, during steady-state ergometer exercise at 0, 30, 50, and 70% of maximum workload, RC distortions were small because of a coordinated action of respiratory muscles, so that net pressures acting on RCp and RCa were nearly the same throughout the respiratory cycle. This maximizes RC compliance and minimizes the work of RC displacement. During quiet breathing, plots of RCa volume vs. abdominal pressure were to the right of the relaxation curve, indicating an expiratory action on RCa. We attribute this to passive stretching of abdominal muscles, which more than counterbalances the insertional component of transdiaphragmatic pressure.

Human respiratory muscle actions and control during exercise.

We measured pressures and power of diaphragm, rib cage, and abdominal muscles during quiet breathing (QB) and exercise at 0, 30, 50, and 70% maximum workload (Wmax) in five men. By three-dimensional tracking of 86 chest wall markers, we calculated the volumes of lung- and diaphragm-apposed rib cage compartments (Vrc,p and Vrc,a, respectively) and the abdomen (Vab). End-inspiratory lung volume increased with percentage of Wmax as a result of an increase in Vrc,p and Vrc,a. End-expiratory lung volume decreased as a result of a decrease in Vab. DeltaVrc,a/DeltaVab was constant and independent of Wmax. Thus we used DeltaVab/time as an index of diaphragm velocity of shortening. From QB to 70% Wmax, diaphragmatic pressure (Pdi) increased approximately 2-fold, diaphragm velocity of shortening 6.5-fold, and diaphragm workload 13-fold. Abdominal muscle pressure was approximately 0 during QB but was equal to and 180 degrees out of phase with rib cage muscle pressure at all percent Wmax. Rib cage muscle pressure and abdominal muscle pressure were greater than Pdi, but the ratios of these pressures were constant. There was a gradual inspiratory relaxation of abdominal muscles, causing abdominal pressure to fall, which minimized Pdi and decreased the expiratory action of the abdominal muscles on Vrc,a gradually, minimizing rib cage distortions. We conclude that from QB to 0% Wmax there is a switch in respiratory muscle control, with immediate recruitment of rib cage and abdominal muscles. Thereafter, a simple mechanism that increases drive equally to all three muscle groups, with drive to abdominal and rib cage muscles 180 degrees out of phase, allows the diaphragm to contract quasi-isotonically and act as a flow generator, while rib cage and abdominal muscles develop the pressures to displace the rib cage and abdomen, respectively. This acts to equalize the pressures acting on both rib cage compartments, minimizing rib cage distortion.

Respiratory dynamics during laughter.

Lung and chest wall mechanics were studied during fits of laughter in 11 normal subjects. Laughing was naturally induced by showing clips of the funniest scenes from a movie by Roberto Benigni. Chest wall volume was measured by using a three-dimensional optoelectronic plethysmography and was partitioned into upper thorax, lower thorax, and abdominal compartments. Esophageal (Pes) and gastric (Pga) pressures were measured in seven subjects. All fits of laughter were characterized by a sudden occurrence of repetitive expiratory efforts at an average frequency of 4.6 +/- 1.1 Hz, which led to a final drop in functional residual capacity (FRC) by 1.55 +/- 0.40 liter (P < 0.001). All compartments similarly contributed to the decrease of lung volumes. The average duration of the fits of laughter was 3.7 +/- 2.2 s. Most of the events were associated with sudden increase in Pes well beyond the critical pressure necessary to generate maximum expiratory flow at a given lung volume. Pga increased more than Pes at the end of the expiratory efforts by an average of 27 +/- 7 cmH2O. Transdiaphragmatic pressure (Pdi) at FRC and at 10% and 20% control forced vital capacity below FRC was significantly higher than Pdi at the same absolute lung volumes during a relaxed maneuver at rest (P < 0.001). We conclude that fits of laughter consistently lead to sudden and substantial decrease in lung volume in all respiratory compartments and remarkable dynamic compression of the airways. Further mechanical stress would have applied to all the organs located in the thoracic cavity if the diaphragm had not actively prevented part of the increase in abdominal pressure from being transmitted to the chest wall cavity.