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Biomedical subjects

R Ginanni

Publications and source records attributed to R Ginanni.

18 recordsLinked to original sources
PubMed2002

Effect of assist negative pressure ventilation by microprocessor based iron lung on breathing effort.

BACKGROUND: The lack of patient triggering capability during negative pressure ventilation (NPV) may contribute to poor patient synchrony and induction of upper airway collapse. This study was undertaken to evaluate the performance of a microprocessor based iron lung capable of thermistor triggering. METHODS: The effects of NPV with thermistor triggering were studied in four normal subjects and six patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) by measuring: (1) the time delay (TDtr) between the onset of inspiratory airflow and the start of assisted breathing; (2) the pressure-time product of the diaphragm (PTPdi); and (3) non-triggering inspiratory efforts (NonTrEf). In patients the effects of negative extrathoracic end expiratory pressure (NEEP) added to NPV were also evaluated. RESULTS: With increasing trigger sensitivity the mean (SE) TDtr ranged from 0.29 (0.02) s to 0.21 (0.01) s (mean difference 0.08 s, 95% CI 0.05 to 0.12) in normal subjects and from 0.30 (0.02) s to 0.21 (0.01) s (mean difference 0.09 s, 95% CI 0.06 to 0.12) in patients with COPD; NonTrEf ranged from 8.2 (1.8)% to 1.2 (0.1)% of the total breaths in normal subjects and from 11.8 (2.2)% to 2.5 (0.4)% in patients with COPD. Compared with spontaneous breathing, PTPdi decreased significantly with NPV both in normal subjects and in patients with COPD. NEEP added to NPV resulted in a significant decrease in dynamic intrinsic PEEP, diaphragm effort exerted in the pre-trigger phase, and NonTrEf. CONCLUSIONS: Microprocessor based iron lung capable of thermistor triggering was able to perform assist NPV with acceptable TDtr, significant unloading of the diaphragm, and a low rate of NonTrEf. NEEP added to NPV improved the synchrony between the patient and the ventilator.

Adult↗
PubMed2001

Physiologic effects of negative pressure ventilation in acute exacerbation of chronic obstructive pulmonary disease.

To assess the physiologic effects of continuous negative extrathoracic pressure (CNEP), negative pressure ventilation (NPV), and negative extrathoracic end-expiratory pressure (NEEP) added to NPV in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD), we measured in seven patients ventilatory pattern, arterial blood gases, respiratory mechanics, and pressure- time product of the diaphragm (PTPdi) under four conditions: (1) spontaneous breathing (SB); (2) CNEP (-5 cm H(2)O); (3) NPV; (4) NPV plus NEEP. CNEP and NPV were provided by a microprocessor-based iron lung capable of thermistor-triggering. Compared with SB, CNEP improved slightly but significantly Pa(CO(2 ))and pH, and decreased PTPdi (388 +/- 59 versus 302 +/- 43 cm H(2)O. s, respectively, p < 0.05) and dynamic intrinsic positive end-expiratory pressure (PEEPi) (4.6 +/- 0.5 versus 2.1 +/- 0.3 cm H(2)O, respectively, p < 0.001). NPV increased minute ventilation (V E), improved arterial blood gases, and decreased PTPdi to 34% of value during SB (p < 0.001). NEEP added to NPV further slightly decreased PTPdi and improved patient-ventilator interaction by reducing dynamic PEEPi and nontriggering inspiratory efforts. We conclude that CNEP and NPV, provided by microprocessor-based iron lung, are able to improve ventilatory pattern and arterial blood gases, and to unload inspiratory muscles in patients with acute exacerbation of COPD.

Acute Disease↗
PubMed2000

Ventilatory and respiratory muscle responses to hypercapnia in patients with paraplegia.

To evaluate ventilatory and respiratory muscle responses to hypercapnia in patients with paraplegia with paralysis of abdominal muscles, we studied seven patients with complete transection of the midthoracic cord (Th6-Th7) and six normal subjects. Minute ventilation (V E) and mean inspiratory flow responses to hypercapnia were similar in normal subjects and patients with paraplegia, but in the latter, at any given level of end-tidal CO(2) partial pressure (PET(CO(2))), tidal volume (VT) was reduced and frequency was increased. In normal subjects during hypercapnia, end-expiratory transpulmonary pressure (PL) and abdominal volume at end expiration decreased markedly, whereas end-expiratory volume of the rib cage (Vrc,E) remained constant, suggesting progressive recruitment of abdominal muscles. In patients with paraplegia compared to normal subjects the decrease in end-expiratory PL was reduced, and it was associated with a decrease in Vrc,E, suggesting recruitment of rib cage expiratory muscles. For a PET(CO(2)) of 70 mm Hg the estimated expiratory muscle contribution to VT was 10.3 and 28.4% (p < 0.02) in patients with paraplegia and normal subjects, respectively. We conclude that the V E-CO(2) relationship is preserved in patients with paraplegia with the development of a rapid and shallow pattern of breathing. This suggests that expiratory muscle paralysis elicits adaptation of the ventilatory control system similar to that observed in patients with generalized respiratory muscle weakness.

Adult↗
PubMed1998

Effect on lung function of methotrexate and non-steroid anti-inflammatory drugs in children with juvenile rheumatoid arthritis.

We evaluated lung function in a group of patients affected by juvenile rheumatoid arthritis (JRA), without clinical and/or radiological signs of respiratory involvement. We compared the effects on pulmonary function of methotrexate (MTX) therapy combined with non-steroid anti-inflammatory drugs (NSAIDs) to those of NSAIDs alone and correlated lung function to subtype onset, disease duration and disease activity. Our patients were 27 JRA children, subdivided into two groups according to the therapy (group A = 14 patients, treated with a low dose of MTX and NSAIDs; group B = 13 patients, treated with NSAIDs alone). Clinical evaluation, haematological data and pulmonary function tests (PFTs) were obtained in each group at baseline (time 0) and at 1 year (time 1). At time 0 and time 1 PFTs were altered in 51.8% of JRA patients. The restrictive pattern (reduced forced vital capacity, FVC) was the most frequent feature, observed in 22.2% of patients. In group A the mean values of FVC, FEV1 (forced expiratory flow in 1 s), FRC (functional residual capacity), TLC (total lung capacity) and DLCO (diffusing lung capacity of carbon monoxide) were significantly lower compared to those of group B, at time 0 and at time 1. No functional parameter was correlated to subtype, duration or activity of the disease. Our study confirms that abnormalities in PFTs may be detected in JRA patients, even in the absence of clinical and/or radiological signs of lung disease; MTX in combination with NSAIDs does not seem to affect lung function at 1 year more than NSAIDs alone.

Adolescent↗
PubMed1998

Negative pressure ventilation versus conventional mechanical ventilation in the treatment of acute respiratory failure in COPD patients.

This case-control study was aimed to evaluate the effectiveness of negative pressure ventilation (NPV) versus conventional mechanical ventilation (CMV) for the treatment of acute respiratory failure (ARF) in patients with chronic obstructive pulmonary disease (COPD) admitted to a respiratory intermediate intensive care unit (RIICU) and four general intensive care units (ICU). Twenty-six COPD patients in ARF admitted in 1994-95 to RIICU and treated with NPV (cases) were matched according to age (+/-5 yrs), sex, causes triggering ARF, Acute Physiology and Chronic Health Evaluation (APACHE) II score (+/- 5 points), pH (+/-0.05) and arterial carbon dioxide tension (Pa,CO2) on admission with 26 patients admitted to ICU and treated with CMV (controls). The primary end points of the study were inhospital death for both groups and the need for endotracheal intubation for cases. The secondary endpoints were length and complications of mechanical ventilation and length of hospital stay. The effectiveness of matching was 91%. Mortality rate was 23% for cases and 27% for controls (NS), five cases needed endotracheal intubation, four of whom subsequently died. The duration of ventilation in survivors was significantly lower in cases than in controls, with a median of 16 h (range 2-111) versus 96 h (range 12-336) (P<0.02), whereas the length of hospital stay was similar in the two groups, with a median of 12 days (range 2-47) for cases vs 12 days (range 3-43) (NS) for controls. No complications were observed in cases, whereas three controls developed infective complications. These results suggest that negative pressure ventilation is as efficacious as conventional mechanical ventilation for the treatment of acute respiratory failure in patients with chronic obstructive pulmonary disease and that it is associated with a shorter duration of ventilation and a similar length of hospital stay compared with conventional mechanical ventilation.

Acute Disease↗
PubMed1996

Intermittent negative pressure ventilation in the treatment of hypoxic hypercapnic coma in chronic respiratory insufficiency.

BACKGROUND: In recent years non-invasive ventilatory techniques have been used successfully in the treatment of acute on chronic respiratory failure (ACRF), but careful selection of patients is essential and a comatose state may represent an exclusion criterion. The aim of this retrospective and uncontrolled study was to evaluate whether a non-invasive ventilatory technique such as the iron lung could also be used successfully in patients with hypoxic hypercapnic coma, thus widening the range for application of non-invasive ventilatory techniques. METHODS: A series of 150 consecutive patients with ACRF and hypoxic hypercapnic coma admitted to our respiratory intensive care unit were evaluated retrospectively. The most common underlying condition was chronic obstructive pulmonary disease (79%). On admission a severe hypoxaemia (Pao2 5.81 (3.01) kPa) and hypercapnia (Paco2 14.88 (2.78) kPa) associated with a decompensated acidosis (pH 7.13 (0.13)) were present, the Glasgow coma score ranged from 3 to 8, and the mean APACHE II score was 31.6 (5.3). All patients underwent intermittent negative pressure ventilation with the iron lung. The study end point was based on a dichotomous classification of treatment failure (defined as death or need for endotracheal intubation) versus therapeutic success. RESULTS: There were 45 treatment failures (30%) and 36 deaths (24%). Nine patients (6%) required intubation because of lack of airway control. The median total duration of ventilation was 27 hours per patient (range 2-274). The 105 successfully treated cases recovered consciousness after a median of four hours (range 1-90) of continuous ventilatory treatment and were discharged after 12.1 (9.0) days. CONCLUSIONS: These results show that, in patients with acute on chronic respiratory failure and hypoxic hypercapnic coma, the iron lung resulted in a high rate of success. As this study has the typical limitations of all retrospective and uncontrolled studies, the results need to be formally confirmed by controlled prospective studies. Confirmation of these results could widen the range of application of non-invasive ventilatory techniques.

Aged↗
PubMed1995

Peri-operative assessment of glomerular permeability.

Surgical trauma may provoke an increase in glomerular permeability. Microalbuminuria is a subclinical increase in urinary albumin ranging from 20 to 300 mg..-1. This cannot be measured with routine laboratory tests and is estimated by radioimmunoassay. It has been proposed that microalbuminuria, an expression of increased glomerular permeability, serves to reflect a generalised increase in systemic vascular permeability. In this study the degree of microalbuminuria (expressed as microalbuminuria/creatinine ratio to correct for dilutional changes) has been measured in two groups of patients undergoing either videolaparoscopic surgery (group A) or conventional, open, abdominal surgery (group B). The anaesthetic technique was standardised and the duration of surgery similar in the two groups. A significant increase (p < 0.01) in the microalbuminuria/urinary creatinine ratio occurred in patients undergoing open abdominal surgery (group B). This alteration appeared 2 h after surgery but had disappeared 24 h after the end of the operation. During surgery, there was a direct relationship between glomerular permeability and the severity of the surgical insult.

Abdomen↗
PubMed1995

Protective effect of sodium cromoglycate on lipopolysaccharide-induced bronchial obstruction in asthmatics.

Lipopolysaccharides (LPS, the major part of endotoxins) are bacterial proinflammatory substances which can induce in asthmatic patients after inhalation a bronchial obstruction with an increase in both histamine bronchial hyperresponsiveness and blood inflammatory markers. The aim of the present study was to evaluate whether an acute inhalation of sodium cromoglycate, an anti-inflammatory and membrane-stabilizating agent, can block the LPS-induced lung function response. Using a double-blind placebo-controlled crossover method, 7 asthmatic subjects were submitted, at 4 days' interval, to a bronchial challenge test with either solvent solution or LPS (20 micrograms) preceded by inhalation of sodium cromoglycate (10 mg) or placebo. Compared to the solvent reaction, LPS induced a significant bronchial obstruction [measured by both the forced expiratory volume in 1 s (FEV1) and the airway resistances] beginning at the 60th minute and lasting more than 300 min (p < 0.01, 2-way ANOVA). On the other hand, acute pretreatment with sodium cromoglycate significantly inhibited the LPS-induced bronchial obstruction. The total lung capacity did not change significantly after LPS inhalation. Thus, this study showed that in asthmatics the LPS-induced FEV1 response is blocked by acute treatment with sodium cromoglycate. Sodium cromoglycate could be an active treatment in asthmatics exposed to house dust containing endotoxin.

Administration, Inhalation↗
PubMed1994

Iron lung treatment of acute on chronic respiratory failure: 16 yrs of experience.

Noninvasive ventilatory supports are gaining a prominent position among ventilatory techniques aimed to improve ventilation in patients with acute-on-chronic respiratory failure (ACRF). It has not yet been established whether these techniques can be considered as a preventive measure to avoid the need for endotracheal intubation, or are really another means to provide full ventilatory support. At our respiratory intensive care unit (RICU), the ventilatory treatment of ACRF has, for many years, been based on a conservative method, which relies on the use of a body ventilator (iron lung) providing intermittent negative pressure ventilation (INPV). From 1975 to 1991, we treated ACRF in 2,116 patients with chronic obstructive pulmonary disease (COPD) and 604 patients with restrictive thoracopulmonary disease (RTD). Two thousand and eleven patients (95%) underwent INPV. The mortality rate during hospitalization was 9.9% for the patients as a whole (10% and 8.9% for COPD and RTD patients, respectively). The mean length of stay in the RICU was 10.5 +/- 9.5 days. Furthermore, we report the results of our previous studies which investigated how the iron lung works, and how it affected the short- and long-term prognosis of COPD patients in ACRF. Finally, in 180 patients, we report the effects of INPV provided by iron lung on the treatment of ACRF with hypoxic hypercapnic coma (HHC). INPV resulted in a significant improvement of arterial blood gas values and pH, associated with a progressive recovery of the level of consciousness. Only 13 patients needed intubation and 41 (23%) died during hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Relation between the bronchial obstructive response to inhaled lipopolysaccharide and bronchial responsiveness to histamine.

BACKGROUND: Bronchoconstriction has developed after inhalation of lipopolysaccharide in a dose of 20 micrograms in asthmatic patients and of 200 micrograms in normal subjects. This study set out to determine whether the bronchial response to lipopolysaccharide was related to non-specific bronchial responsiveness and atopy. METHODS: Sixteen subjects with a fall in specific airway conductance of 40% (PD40sGaw) after inhaling up to 900 micrograms histamine inhaled 20 micrograms lipopolysaccharide (from Escherichia coli type 026:B6) a week after bronchial challenge with a control solution of saline. The bronchial response over five hours was measured as change in FEV1 and area under the FEV1-time curve. RESULTS: FEV1 fell significantly more after lipopolysaccharide than after diluent inhalation, the difference in mean (SE) FEV1 being 4.6% (5.4%); response was maximal 60 minutes after lipopolysaccharide inhalation and lasted more than five hours. Histamine PD20FEV1 and PD40sGaw correlated with the fall in FEV1 after lipopolysaccharide inhalation. There was no difference in the proportions of responders and non-responders to lipopolysaccharide who were atopic. CONCLUSION: Lipopolysaccharide induced bronchial obstruction is associated with non-specific responsiveness but not with atopy.

Administration, Inhalation↗
PubMed1992

Inflammatory response to acute inhalation of endotoxin in asthmatic patients.

Inhalation of 20 micrograms endotoxins (from the membrane of Gram-negative bacteria) has been reported to induce a bronchial obstructive response in asthmatic subjects. The aim of the present study was to evaluate in asthmatic patients the possibility of an inflammatory response to inhaled endotoxins. Eight patients with mild asthma were submitted to bronchial challenge tests, in a single-blind trial, on Day 1 with control solution and on Day 7 with 20 micrograms endotoxin of Escherichia coli (026:B6). Local inflammatory response was indirectly evaluated by the degree of bronchial hyperresponsiveness (BHR) expressed as PD20 FEV1 histamine (the dose of histamine inducing a 20% decrease in FEV1) at 0, 6, 24, and 48 h and 7 days. Systemic inflammation was investigated by sequential blood determinations of total (and differential) white cells, complement anaphylatoxin C5a, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and C-reactive protein (CRP). A significant (p < 0.01) bronchial obstructive response was demonstrable 45 min after lipopolysaccharide (LPS) inhalation, lasting 5 h. Comparing the level of BHR after control inhalation, a significant (p < 0.05) increase in BHR was shown 6 h after LPS, partially normalized at 24 and 48 h. A short peak in TNF-alpha at 60 min (p < 0.05) and an increase in total white blood cells (p < 0.01) and neutrophil polymorphonuclear neutrophils at 360 min (p < 0.05) and of CRP at 24 and 48 h (p < 0.05 and p < 0.01) were significant. The other blood parameters did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

Domestic endotoxin exposure and clinical severity of asthma.

Endotoxins are potent pro-inflammatory substances present in several natural environments and in commercial house dust extracts. To investigate the possible effect of chronic endotoxin exposure on asthma, 28 patients with perennial chronic asthma (20 allergic to house dust mite and eight intrinsic asthmatics) were evaluated during a 4-month period (lung function, clinical and immunological criteria). At the same time, two house dust samples were collected from each patient's home to determine total house dust weight (mg/m2), endotoxin concentration and house dust mite antigen content (evaluated indirectly by guanine content with HPLC method). The mean (+/- s.d.) endotoxin concentration, as measured by quantitative Limulus assay was 2.59 (+/- 3.41) ng/mg house dust, ranging from 0.12 to 20 ng/mg. The mean guanine content was 0.13 (+/- 0.16) mg/100 mg house dust. There was no correlation between endotoxin and house dust mite concentrations. Patients were compared according to the low or high grade exposure to dust, endotoxins and guanine. Compared with patients with low grade (less than or equal to 5.6 ng/ml) exposure, subjects exposed to high endotoxin concentrations (greater than 5.6 ng/ml) showed a significant increase in dyspnea (median 2.6 vs 3.3; P less than 0.05) and treatment (median 14 vs 44.3; P less than 0.01) scores, oral corticosteroid (median 0.0 vs 13.5 mg/24 hr; P less than 0.01) and beta 2-mimetics (median four vs eight puffs/day; P less than 0.01) intake, and a significant decrease in FEV1/FVC (median 84.5 vs 67% of predicted value; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effect of endotoxin contamination on the antigenic skin test response.

Bacterial lipopolysaccharides (LPS), the major part of endotoxin, are proinflammatory substances present in the natural environment. Lipopolysaccharides enhance allergen-induced histamine release from human basophils of allergic subjects. The aim of this study was to assess the LPS activity on the allergy skin test response. Twenty patients allergic to house dust mite (HDM) underwent skin prick tests with LPS (E coli 026: B6 serotype) at concentrations of 1, 10, 100 micrograms/mL, with HDM extracts at different dilutions, and with solutions of LPS mixed with HDM. Endotoxin alone did not induce any immediate skin response; LPS had a synergistic effect on the HDM skin response both in terms of flare [27.4 +/- 2.8 mm, 26.6 +/- 3.3 mm, 28.1 +/- 2.5 mm versus 20.7 +/- 3.6 mm, respectively in presence of LPS 1 (P less than .02), 10 (P less than .05), 100 (P less than .01) micrograms/mL] and wheal response [6.4 +/- 1.0 mm, in presence of LPS 100 micrograms/mL versus 4.9 +/- 1.1 mm in absence of LPS (P less than .05)]. On the other hand, a possible LPS synergistic action on the histamine skin response was evaluated in ten normal subjects but the results were not significant. These findings show that LPS increases the allergy skin response probably due to a mechanism including a potentiation of the IgE receptor activation rather than an increase of the skin response to the release mediators.

Adult↗
PubMed1990

Inspiratory muscle strength and respiratory drive in patients with rheumatoid arthritis.

In 15 patients with rheumatoid arthritis (RA) and in 12 age- and sex-matched normal subjects, we evaluated inspiratory muscle strength and respiratory control system. Inspiratory muscle strength was assessed by measuring maximal inspiratory pressure (MIP). Respiratory drive was assessed by evaluating surface electromyographic activity of the diaphragm (EMGd) during both room-air breathing and hypercapnic rebreathing. Compared to the predicted value (mean +/- 1.65 SD), MIP was significantly reduced in nine patients (60%). All told, we noticed a significant inverse relationship in the patients between MIP and duration of steroid therapy (p less than 0.01). During room-air breathing, both EMGd and mouth occlusion pressure (P0.1), expressed both in actual values and as percentage of MIP, were significantly greater in patients than in the normal control group (p less than 0.001 for both). Both EMGd and P0.1 (%MIP) response slopes to CO2 were significantly greater in patients than in the normal control group (p less than 0.01 and p less than 0.001, respectively) and significantly related to the functional stage of disease. During quiet breathing and for a PETCO2 of 60 mm Hg, both EMGd (p less than 0.01 and p less than 0.05, respectively) and P0.1 (%MIP) (p less than 0.01 and p = 0.001, respectively) were inversely related to MIP. These results indicate that RA patients may exhibit inspiratory muscle weakness and increased respiratory drive. Steroid myopathy and rheumatoid myositis could explain the reduction in MIP, whereas neural afferents arising from respiratory muscle, lung, or joint receptors could be involved in the observed increase in neural drive.

Arthritis, Rheumatoid↗
PubMed1990

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.

Aged↗
PubMed1989

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.

Aged↗