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1.
Inhal Toxicol ; 33(2): 55-65, 2021 02.
Article in English | MEDLINE | ID: mdl-33622153

ABSTRACT

PURPOSE: Limited number of studies investigated the effects of Electrostatic powder paints (EPP) on human health. We investigated the effects of EPP exposure on lung function, exercise capacity, and quality of life, and the factors determining exercise capacity in EPP workers. METHODS: Fifty-four male EPP workers and 54 age-matched healthy male individuals (control group) were included. Lung function and respiratory muscle strength were measured. The lower limit of normal (LLN) cut-points for FEV1 and FEV1/FVC were calculated. An EPT was used to evaluate bronchial hyperactivity. The handgrip and quadriceps muscle strength were evaluated using a hand-held dynamometer. An ISWT was used to determine exercise capacity. The physical activity level was questioned using the IPAQ. The SGRQ and NHP were used to assessing respiratory specific and general quality of life, respectively. RESULTS: Duration of work, FEV1, MIP, handgrip strength, and ISWT distance were significantly lower, and the change in FEV1 after EPT and %HRmax were significantly higher in the EPP group compared to the control group (p < 0.05). There were no subjects with a < LLN for FEV1 and FEV1/FVC in both groups. In the EPP group, ISWT distance was significantly related to age, height, duration of work, FEV1, change in FEV1 after EPT, MIP, MEP, handgrip strength, IPAQ, SGRQ, and NHP total scores (p < 0.05). The change in FEV1 after EPT, MIP, and duration of work explained % 62 of the variance in the ISWT distance (p < 0.001). CONCLUSIONS: Changes in lung function based on LLN for the FEV1 and FEV1/FVC were not clinically relevant in EPP workers. Exercise capacity is impaired in EPP workers. Degree of exercise-induced bronchospasm, inspiratory muscle strength, and duration of work are the determinants of exercise capacity in EPP workers.


Subject(s)
Exercise Tolerance/drug effects , Occupational Exposure , Paint/analysis , Polyesters/toxicity , Powders/toxicity , Respiratory Muscles/drug effects , Adult , Case-Control Studies , Humans , Male , Muscle Strength/drug effects , Paint/adverse effects , Polyesters/administration & dosage , Polyesters/analysis , Powders/administration & dosage , Powders/adverse effects , Respiratory Function Tests , Walking , Young Adult
2.
Pediatr Pulmonol ; 56(1): 299-306, 2021 01.
Article in English | MEDLINE | ID: mdl-33118682

ABSTRACT

INTRODUCTION: Nusinersen is associated with an improvement in motor function in children with spinal muscular atrophy (SMA) but data on respiratory muscles strength are scarce. Respiratory muscles performance and lung function were evaluated in children with SMA 1c and 2 after six injections of nusinersen (M14). Results from patients with SMA2 were compared with data of age-matched historical controls. Motor function tests (MFM and HINE-2) were assessed at baseline and M14 in the treated patients. RESULTS: Sixteen children (2 SMA Type 1c and 14 SMA Type 2), mean age 9.4 ± 2.3 years, were included. The data of 14 historical SMA 2 controls (mean age 9.3 ± 1.9 years) were gathered. The strength of the global inspiratory muscles of SMA 2 treated with nusinersen, assessed on maximal static inspiratory pressure, forced vital capacity, and esophageal pressure during a maximal sniff was significantly better compared with historical controls (p < .05). A significant improvement in MFM and HINE-2 was observed in the patients with 16 SMA treated with nusinersen after 14 months as compared with baseline. CONCLUSION: In children with SMA Type 2, respiratory muscle performance was significantly better after six injections of nusinersen as compared with age-matched SMA Type 2 historical controls.


Subject(s)
Motor Skills/drug effects , Oligonucleotides/therapeutic use , Respiratory Muscles/drug effects , Spinal Muscular Atrophies of Childhood/drug therapy , Child , Child, Preschool , Female , Historically Controlled Study , Humans , Male , Oligonucleotides/pharmacology , Respiratory Function Tests , Respiratory Muscles/physiopathology , Spinal Muscular Atrophies of Childhood/physiopathology
3.
Mol Med ; 26(1): 58, 2020 06 16.
Article in English | MEDLINE | ID: mdl-32546125

ABSTRACT

In light of the present therapeutic situation in COVID-19, any measure to improve course and outcome of seriously affected individuals is of utmost importance. We recap here evidence that supports the use of human recombinant erythropoietin (EPO) for ameliorating course and outcome of seriously ill COVID-19 patients. This brief expert review grounds on available subject-relevant literature searched until May 14, 2020, including Medline, Google Scholar, and preprint servers. We delineate in brief sections, each introduced by a summary of respective COVID-19 references, how EPO may target a number of the gravest sequelae of these patients. EPO is expected to: (1) improve respiration at several levels including lung, brainstem, spinal cord and respiratory muscles; (2) counteract overshooting inflammation caused by cytokine storm/ inflammasome; (3) act neuroprotective and neuroregenerative in brain and peripheral nervous system. Based on this accumulating experimental and clinical evidence, we finally provide the research design for a double-blind placebo-controlled randomized clinical trial including severely affected patients, which is planned to start shortly.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/prevention & control , Erythropoietin/therapeutic use , Neuroprotective Agents/therapeutic use , Pneumonia, Viral/drug therapy , Respiratory System Agents/therapeutic use , Brain Stem/drug effects , Brain Stem/immunology , Brain Stem/virology , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/virology , Double-Blind Method , Humans , Lung/drug effects , Lung/immunology , Lung/virology , Pandemics , Phrenic Nerve/drug effects , Phrenic Nerve/immunology , Phrenic Nerve/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Proof of Concept Study , Randomized Controlled Trials as Topic , Recombinant Proteins/therapeutic use , Respiratory Muscles/drug effects , Respiratory Muscles/immunology , Respiratory Muscles/virology , SARS-CoV-2 , Severity of Illness Index , Spinal Cord/drug effects , Spinal Cord/immunology , Spinal Cord/virology
4.
Anaesthesia ; 75(3): 338-347, 2020 03.
Article in English | MEDLINE | ID: mdl-31420989

ABSTRACT

Obstructive sleep apnoea and residual neuromuscular blockade are, independently, known to be risk factors for respiratory complications after major surgery. Residual effects of neuromuscular blocking agents are known to reduce the hypoxic ventilatory response in healthy volunteers. Patients with obstructive sleep apnoea have impaired control of breathing, but it is not known to what extent neuromuscular blocking agents interfere with the regulation of breathing in such patients. In a physiological study in 10 unsedated men with untreated obstructive sleep apnoea, we wished to examine if partial neuromuscular blockade had an effect on hypoxic ventilatory response (isocapnic hypoxia to oxygen saturation of 80%) and hypercapnic ventilatory response (normoxic inspired carbon dioxide 5%). The hypoxic ventilatory response was reduced by 32% (p = 0.016) during residual neuromuscular block (rocuronium to train-of-four ratio 0.7), but the hypercapnic ventilatory response was unaffected. We conclude that neuromuscular blockade specifically depresses peripheral chemosensitivity, and not respiratory muscle function since the hypercapnic ventilatory response was unaffected.


Subject(s)
Hypoxia/chemically induced , Hypoxia/physiopathology , Neuromuscular Blockade/adverse effects , Neuromuscular Nondepolarizing Agents/adverse effects , Pulmonary Ventilation , Rocuronium/adverse effects , Sleep Apnea, Obstructive/physiopathology , Adolescent , Adult , Aged , Carbon Dioxide/blood , Humans , Hypercapnia/physiopathology , Male , Middle Aged , Oxygen/blood , Prospective Studies , Respiratory Muscles/drug effects , Respiratory Muscles/physiopathology , Risk Factors , Young Adult
5.
Intensive Care Med ; 45(10): 1372-1381, 2019 10.
Article in English | MEDLINE | ID: mdl-31576436

ABSTRACT

PURPOSE: Respiratory muscle weakness frequently develops in critically ill patients and is associated with adverse outcome, including difficult weaning from mechanical ventilation. Today, no drug is approved to improve respiratory muscle function in these patients. Previously, we have shown that the calcium sensitizer levosimendan improves calcium sensitivity of human diaphragm muscle fibers in vitro and contractile efficiency of the diaphragm in healthy subjects. The main purpose of this study is to investigate the effects of levosimendan on diaphragm contractile efficiency in mechanically ventilated patients. METHODS: In a double-blind randomized placebo-controlled trial, mechanically ventilated patients performed two 30-min continuous positive airway pressure (CPAP) trials with 5-h interval. After the first CPAP trial, study medication (levosimendan 0.2 µg/kg/min continuous infusion or placebo) was administered. During the CPAP trials, electrical activity of the diaphragm (EAdi), transdiaphragmatic pressure (Pdi), and flow were measured. Neuromechanical efficiency (primary outcome parameter) was calculated. RESULTS: Thirty-nine patients were included in the study. Neuromechanical efficiency was not different during the CPAP trial after levosimendan administration compared to the CPAP trial before study medication. Tidal volume and minute ventilation were higher after levosimendan administration (11 and 21%, respectively), whereas EAdi and Pdi were higher in both groups in the CPAP trial after study medication compared to the CPAP trial before study medication. CONCLUSIONS: Levosimendan does not improve diaphragm contractile efficiency.


Subject(s)
Respiratory Muscles/drug effects , Simendan/pharmacology , Ventilator Weaning/methods , Critical Illness/therapy , Double-Blind Method , Electromagnetic Phenomena , Humans , Muscle Weakness/etiology , Muscle Weakness/physiopathology , Pressure , Respiration, Artificial/methods , Simendan/therapeutic use , Ventilator Weaning/standards , Ventilator Weaning/trends
6.
BMC Anesthesiol ; 19(1): 187, 2019 10 19.
Article in English | MEDLINE | ID: mdl-31629404

ABSTRACT

BACKGROUND: The use of neostigmine after neuromuscular blockade (NMB) has been associated with postoperative respiratory complications. In previous studies, we found lower diaphragmatic activity after neostigmine reversal of NMB, compared to sugammadex. It is still unclear whether the adequate use of neostigmine guarantees normal respiratory muscle function after NMB. In this study, we wanted to assess the effect of commonly used degrees of NMB and their possible reversal strategies on respiratory muscle activity after the return of normal neuromuscular transmission. METHODS: This is a randomized, controlled, parallel-group, single-centre, double-blind study in patients scheduled for intracranial surgery at a tertiary academic hospital in Belgium. All participants received target controlled propofol/remifentanil anesthesia and were randomized into one of five groups, receiving either a shallow NMB with no reversal (shallow/saline), a shallow NMB with sugammadex reversal (shallow/sugammadex), a moderate NMB with neostigmine reversal (moderate/neostigmine), a moderate NMB with sugammadex reversal (moderate/sugammadex), or a deep NMB with sugammadex reversal (deep/sugammadex). Primary and secondary outcome parameters were diaphragm and intercostal electromyographic (EMG) activity at the moment of resumed spontaneous breathing activity, defined as a maximal interval of 10 min after the first spontaneous breath. RESULTS: For the five groups, a total of 55 patients could be included in the final analysis. Median time of spontaneous breathing analyzed was 5 min (IQR 3-9.5 min). Both the moderate/sugammadex and the moderate/neostigmine groups had lower levels of diaphragm EMG compared to the shallow/sugammadex group. The moderate/neostigmine group had lower levels of intercostal EMG activity compared to the shallow/saline group. CONCLUSIONS: In this study, the depth of neuromuscular blockade and type of reversal strategy impacts respiratory muscle activity at the moment of resumed spontaneous breathing and recovery of neuromuscular blockade. Both groups that received moderate NMB had lower levels of diaphragm EMG, compared to the shallow NMB group with sugammadex reversal. Compared to the shallow NMB group with no reversal, the moderate NMB with neostigmine reversal group had lower intercostal EMG activity. TRIAL REGISTRATION: Clinicaltrials.gov NCT01962298 on October 9, 2013 and EudraCT 2013-001926-25 on October 10, 2013.


Subject(s)
Neostigmine/administration & dosage , Neuromuscular Blockade/methods , Respiratory Muscles/drug effects , Sugammadex/administration & dosage , Adult , Aged , Double-Blind Method , Electromyography , Female , Humans , Male , Middle Aged , Propofol/administration & dosage , Prospective Studies , Remifentanil/administration & dosage , Respiratory Muscles/physiology , Time Factors
8.
Intensive Care Med ; 45(8): 1061-1071, 2019 08.
Article in English | MEDLINE | ID: mdl-31236639

ABSTRACT

INTRODUCTION: This narrative review summarizes current knowledge on the physiology and pathophysiology of expiratory muscle function in ICU patients, as shared by academic professionals from multidisciplinary, multinational backgrounds, who include clinicians, clinical physiologists and basic physiologists. RESULTS: The expiratory muscles, which include the abdominal wall muscles and some of the rib cage muscles, are an important component of the respiratory muscle pump and are recruited in the presence of high respiratory load or low inspiratory muscle capacity. Recruitment of the expiratory muscles may have beneficial effects, including reduction in end-expiratory lung volume, reduction in transpulmonary pressure and increased inspiratory muscle capacity. However, severe weakness of the expiratory muscles may develop in ICU patients and is associated with worse outcomes, including difficult ventilator weaning and impaired airway clearance. Several techniques are available to assess expiratory muscle function in the critically ill patient, including gastric pressure and ultrasound. CONCLUSION: The expiratory muscles are the "neglected component" of the respiratory muscle pump. Expiratory muscles are frequently recruited in critically ill ventilated patients, but a fundamental understanding of expiratory muscle function is still lacking in these patients.


Subject(s)
Exhalation/physiology , Muscular Diseases/physiopathology , Respiratory Muscles/physiopathology , Critical Illness , Humans , Respiratory Muscles/abnormalities , Respiratory Muscles/drug effects , Work of Breathing/physiology
9.
Pulm Pharmacol Ther ; 56: 1-7, 2019 06.
Article in English | MEDLINE | ID: mdl-30797981

ABSTRACT

The traditional theophylline bronchodilator, aminophylline, is still widely used, especially in the treatment of COPD. The effects of aminophylline on ventilation and action of the costal diaphragm have been previously defined, but other respiratory muscles - notably the chest wall, are not well determined. Therefore, we investigated the effects of aminophylline on the Parasternal intercostal, a key obligatory inspiratory muscle, examining muscle length, shortening and EMG. We studied 11 awake canines, chronically implanted with sonomicrometer crystals and fine-wire EMG electrodes in the parasternal muscle. Ventilatory parameters, muscle length (shortening), and moving average muscle EMG activity, were measured at baseline and with aminophylline, during resting and hypercapnic stimulated breathing. Experiments were carried out prior to administration of aminophylline (baseline), and 1.5 h after loading and ongoing infusion. Minute ventilation, tidal volume and respiratory frequency all increased significantly with aminophylline, both during resting breathing and at equivalent levels of hypercapnic stimulated breathing. Parasternal baseline muscle length was entirely unchanged with aminophylline. Parasternal shortening increased significantly with aminophylline while corresponding parasternal EMG activity remained constant, consistent with increased contractility. Thus, in awake, intact mammals, aminophylline, in the usual therapeutic range, elicits increased ventilation and increased contractility of all primary inspiratory respiratory muscles, including both chest wall and diaphragm.


Subject(s)
Aminophylline/pharmacology , Bronchodilator Agents/pharmacology , Muscle Contraction/drug effects , Respiratory Muscles/drug effects , Animals , Diaphragm/drug effects , Diaphragm/metabolism , Dogs , Electromyography , Male , Respiratory Muscles/metabolism , Thoracic Wall/drug effects , Thoracic Wall/metabolism , Tidal Volume/drug effects , Wakefulness
10.
IEEE J Biomed Health Inform ; 23(6): 2455-2463, 2019 11.
Article in English | MEDLINE | ID: mdl-30676990

ABSTRACT

We propose an extended model of cardiovascular regulation to assess heart rate variability in patients poisoned with organophosphate during their treatment with mechanical ventilation. The model was modified to fit a population of 21 patients poisoned with organophosphorus compounds and undergoing mechanical ventilation. The extended model incorporated the respiratory muscle activity measured by surface electromyography for quantifying the vagal-sympathetic engagement during spontaneous breathing test. The order and structure of the parasympathetic and the sympathetic transfer function with respect to the original model were modified to a second-order system. In this extended model, the parameters related to the vagal-sympathetic response (corner frequency and constant gain) were correlated with respiratory muscle activity. When the diaphragm's contractions were stronger, the sympathetic corner frequency increased while the parasympathetic corner frequency and gain decreased. Thus, the proposed model could be useful to improve the ventilatory support and pharmacological treatment for patients poisoned with organophosphorus compounds considering the vagal-sympathetic response inferred from the respiratory muscle activity.


Subject(s)
Heart Rate/drug effects , Organophosphate Poisoning , Respiratory Muscles , Adult , Electromyography , Female , Humans , Male , Organophosphate Poisoning/diagnosis , Organophosphate Poisoning/physiopathology , Respiratory Muscles/drug effects , Respiratory Muscles/physiopathology , Young Adult
11.
Medicine (Baltimore) ; 98(2): e13982, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30633180

ABSTRACT

Mechanical ventilation may cause diaphragm weakness an effect termed ventilator-induced diaphragm dysfunction (VIDD). The prevalence of VIDD among patients receiving mechanical ventilation is very high, with the degree of diaphragmatic atrophy being associated with the length of mechanical ventilation. Theophylline is known to increase diaphragmatic contractility and reduce fatigue, so in this study, we evaluated the effect of theophylline in patients with prolonged mechanical ventilation.Patients who depended on mechanical ventilation were included in the study. We compared the maximum inspiratory pressure (PImax) values, rapid shallow breathing index (RSBI) values, and successful weaning rates of theophylline-treated and non-theophylline-treated patients.Eighty-four patients received theophylline and 76 patients did not. These 2 groups' clinical characteristics, including their PImax and RSBI at initial admission, were similar. The results showed that the theophylline-treated group had significantly better PImax and RSBI, with a higher last PImax (30.1 ±â€Š9.7 cmH2O vs 26.9 ±â€Š9.1 cmH2O; P = .034) and lower last RSBI (107.0 ±â€Š68.4 vs 131.4 ±â€Š77.7; P = .036). The improvements to each respective patient's PImax and RSBI were also significantly higher in the theophylline-treated group (PImax: 20.1 ±â€Š5.7% vs 3.2 ±â€Š1.1%, P = .005; RSBI: 11.2 ±â€Š3.0% vs 2.7 ±â€Š1.6%, P = .015). The weaning success rate of the theophylline-treated group was also higher, but not significantly so.Theophylline might improve respiratory muscle strength in patients with prolonged mechanical ventilation and it needs further prospective studies to confirm.


Subject(s)
Diaphragm/drug effects , Muscle Strength/drug effects , Theophylline/pharmacology , Ventilator Weaning/statistics & numerical data , Aged , Aged, 80 and over , Humans , Middle Aged , Muscle Contraction/drug effects , Respiration, Artificial , Respiratory Muscles/drug effects , Retrospective Studies
12.
Neuroscience ; 397: 1-11, 2019 01 15.
Article in English | MEDLINE | ID: mdl-30500613

ABSTRACT

The inspiratory motor activities are greater in the intercostal muscles positioned at more rostral thoracic segments. This rostro-caudal gradient of the thoracic inspiratory motor activity is thought to be generated by the spinal interneurons. To clarify the involvement of the inhibitory thoracic interneurons in this rostro-caudal gradient, we examined the effects of 10 µM strychnine, an antagonist of glycine and GABAA receptors, applied to the neonatal rat thoracic spinal cord. The respiratory-related interneuron activities were optically recorded from thoracic segments in the isolated neonatal rat brainstem-spinal cord preparations stained with voltage-sensitive dye, and the electrical inspiratory motor activities were obtained from the third and eleventh thoracic ventral roots (T3VR, T11VR). Although strychnine caused seizure-like activities in all of the ventral roots recorded, the inspiratory motor activities continued. The inspiratory optical signals in the rostral thoracic segments (T2-T5) were significantly larger than those in the caudal thoracic segments (T9-T11) regardless of the existence of strychnine. Similarly, the percent ratio of the amplitude of the inspiratory electrical activity in the T3VR under control and strychnine was significantly larger than that in the T11VR regardless of the existence of strychnine. Strychnine significantly increased the inspiratory activity in both the T3VR and T11VR. These results suggest that the glycinergic and GABAergic inhibitory interneurons are not essential to generate the rostro-caudal gradient in the neonatal rat thoracic inspiratory motor outputs, but these interneurons are likely to play a role in the inhibitory control of inspiratory motor output.


Subject(s)
Inhalation/physiology , Interneurons/physiology , Movement/physiology , Neural Inhibition/physiology , Respiratory Muscles/physiology , Spinal Nerve Roots/physiology , Animals , Animals, Newborn , Brain Stem/drug effects , Brain Stem/physiology , Glycine/metabolism , Inhalation/drug effects , Interneurons/drug effects , Movement/drug effects , Neural Inhibition/drug effects , Neurotransmitter Agents/pharmacology , Rats, Wistar , Receptors, GABA-A/metabolism , Receptors, Glycine/antagonists & inhibitors , Receptors, Glycine/metabolism , Respiratory Muscles/drug effects , Respiratory Muscles/innervation , Seizures/physiopathology , Spinal Nerve Roots/drug effects , Strychnine/pharmacology , Thoracic Vertebrae , Tissue Culture Techniques , Voltage-Sensitive Dye Imaging , gamma-Aminobutyric Acid/metabolism
13.
Respir Physiol Neurobiol ; 260: 114-121, 2019 02.
Article in English | MEDLINE | ID: mdl-30453086

ABSTRACT

This study aimed to investigate whether exercise hyperpnoea contributes to an impairment of locomotor muscle oxygenation and performance during repeated-sprint exercise in normoxia and hypoxia. Subjects performed ten 10-s sprints, separated by 30 s of passive rest while breathing either a normoxic (21% O2) or hypoxic (15% O2) gas mixture. Muscle oxygenation of the vastus lateralis and intercostal muscles was examined with near-infrared spectroscopy. Sprint and recovery vastus lateralis deoxyhaemoglobin was elevated in hypoxia by 9.2% (90% confidence interval 0.2 to 18.0) and 14.1% (90% CL 4.9 to 23.3%) compared to normoxia, respectively. There were no clear differences in respiratory muscle deoxyhaemoglobin (-0.1%, 90% CL -2.9 to 0.9%) or oxyhaemoglobin (0.9%, 90% CL -0.8 to 2.6%) between conditions. Maintenance of respiratory muscle oxygenation may contribute to the rise of vastus lateralis deoxyhaemoglobin in hypoxia during intermittent sprint cycling. This manuscript presents data which extends the fact that oxygen competition could be a limiting factor of exercise capacity.


Subject(s)
Exercise , Hypoxia/pathology , Oxygen/administration & dosage , Respiratory Muscles/drug effects , Respiratory Muscles/metabolism , Adult , Exercise Test , Female , Hemoglobins/metabolism , Humans , Male , Oxygen Consumption/physiology , Oxyhemoglobins/metabolism , Single-Blind Method , Spectroscopy, Near-Infrared , Young Adult
15.
Br J Anaesth ; 121(5): 1156-1165, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30336861

ABSTRACT

BACKGROUND: Driving pressure (ΔP) represents tidal volume normalised to respiratory system compliance (CRS) and is a novel parameter to target ventilator settings. We conducted a study to determine whether CRS and ΔP reflect aerated lung volume and dynamic strain during general anaesthesia. METHODS: Twenty non-obese patients undergoing open abdominal surgery received three PEEP levels (2, 7, or 12 cm H2O) in random order with constant tidal volume ventilation. Respiratory mechanics, lung volumes, and alveolar recruitment were measured to assess end-expiratory aerated volume, which was compared with the patient's individual predicted functional residual capacity in supine position (FRCp). RESULTS: CRS was linearly related to aerated volume and ΔP to dynamic strain at PEEP of 2 cm H2O (intraoperative FRC) (r=0.72 and r=0.73, both P<0.001). These relationships were maintained with higher PEEP only when aerated volume did not overcome FRCp (r=0.73, P<0.001; r=0.54, P=0.004), with 100 ml lung volume increases accompanied by 1.8 ml cm H2O-1 (95% confidence interval [1.1-2.5]) increases in CRS. When aerated volume was greater or equal to FRCp (35% of patients at PEEP 2 cm H2O, 55% at PEEP 7 cm H2O, and 75% at PEEP 12 cm H2O), CRS and ΔP were independent from aerated volume and dynamic strain, with CRS weakly but significantly inversely related to alveolar dead space fraction (r=-0.47, P=0.001). PEEP-induced alveolar recruitment yielded higher CRS and reduced ΔP only at aerated volumes below FRCp (P=0.015 and 0.008, respectively). CONCLUSIONS: During general anaesthesia, respiratory system compliance and driving pressure reflect aerated lung volume and dynamic strain, respectively, only if aerated volume does not exceed functional residual capacity in supine position, which is a frequent event when PEEP is used in this setting.


Subject(s)
Anesthesia, General , Lung Volume Measurements , Respiratory Mechanics/drug effects , Respiratory Muscles/drug effects , Abdomen/surgery , Aged , Female , Functional Residual Capacity , Humans , Lung Compliance , Male , Middle Aged , Peak Expiratory Flow Rate , Positive-Pressure Respiration , Pulmonary Alveoli/drug effects , Supine Position , Tidal Volume
16.
Respir Res ; 19(1): 173, 2018 Sep 12.
Article in English | MEDLINE | ID: mdl-30208912

ABSTRACT

BACKGROUND: Berardinelli-Seip Congenital Generalized Lipodystrophy (BSCL) is an ultra-rare metabolic disease characterized by hypertriglyceridemia, hyperinsulinemia, hyperglycemia, hypoleptinemia, and diabetes mellitus. Although cardiovascular disturbances have been observed in BSCL patients, there are no studies regarding the Respiratory Muscle Strength (RMS) in this type of lipodystrophy. This study aimed to evaluate RMS in BSCL subjects compared with healthy subjects. METHODS: Eleven individuals with BSCL and 11 healthy subjects matched for age and gender were included in this study. The Maximum Inspiratory Pressure (MIP), Maximum Expiratory Pressure (MEP), and Peripheral Muscle Strength (PMS) were measured for three consecutive years. BSCL subjects were compared to healthy individuals for MIP, MEP, and PMS. Correlations between PMS and MIP were also analyzed. The genetic diagnosis was performed, and sociodemographic and anthropometric data were also collected. RESULTS: BSCL subjects showed significantly lower values for MIP and MEP (p <  0.0001 and p = 0.0002, respectively) in comparison to healthy subjects, but no changes in handgrip strength (p = 0.15). Additionally, we did not observe changes in MIP, MEP, and PMS two years after the first analysis, showing maintenance of respiratory dysfunction in BSCL subjects (p = 0.05; p = 0.45; p = 0.99). PMS and MIP were not correlated in these subjects (r = 0.56; p = 0.18). CONCLUSION: BSCL subjects showed lower respiratory muscle strength when compared with healthy subjects; however, PMS was not altered. These findings were maintained at similar levels during the two years of evaluation. Our data reveal the first association of BSCL with the development of respiratory muscle weakness.


Subject(s)
Lipodystrophy, Congenital Generalized/diagnosis , Lipodystrophy, Congenital Generalized/physiopathology , Muscle Strength/physiology , Respiratory Muscles/physiopathology , Adult , Cross-Sectional Studies , Female , Humans , Leptin/analogs & derivatives , Leptin/pharmacology , Leptin/therapeutic use , Lipodystrophy, Congenital Generalized/drug therapy , Longitudinal Studies , Male , Maximal Respiratory Pressures/methods , Muscle Strength/drug effects , Respiratory Muscles/drug effects , Young Adult
17.
J Appl Physiol (1985) ; 125(3): 770-779, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29792554

ABSTRACT

Acetazolamide, a carbonic anhydrase (CA) inhibitor used clinically and to prevent acute mountain sickness, worsens skeletal muscle fatigue in animals and humans. In animals, methazolamide, a methylated analog of acetazolamide and an equally potent CA inhibitor, reportedly exacerbates fatigue less than acetazolamide. Accordingly, we sought to determine, in humans, if methazolamide would attenuate diaphragm and dorsiflexor fatigue compared with acetazolamide. Healthy men (dorsiflexor: n = 12; diaphragm: n = 7) performed fatiguing exercise on three occasions, after ingesting acetazolamide (250 mg three times a day) and then in random order, methazolamide (100 mg twice a day) or placebo for 48 h. For both muscles, subjects exercised at a fixed intensity until exhaustion on acetazolamide, with subsequent iso-time and -workload trials. Diaphragm exercise was performed using a threshold-loading device, while dorsiflexor exercise was isometric. Neuromuscular function was determined pre- and postexercise by potentiated transdiaphragmatic twitch pressure and dorsiflexor torque in response to stimulation of the phrenic and fibular nerve, respectively. Diaphragm contractility 3-10 min postexercise was impaired more for acetazolamide than methazolamide or placebo (82 ± 10, 87 ± 9, and 91 ± 8% of pre-exercise value; P < 0.05). Similarly, dorsiflexor fatigue was greater for acetazolamide than methazolamide (mean twitch torque of 61 ± 11 vs. 57 ± 13% of baseline, P < 0.05). In normoxia, methazolamide leads to less neuromuscular fatigue than acetazolamide, indicating a possible benefit for clinical use or in the prophylaxis of acute mountain sickness. NEW & NOTEWORTHY Acetazolamide, a carbonic anhydrase inhibitor, may worsen diaphragm and locomotor muscle fatigue after exercise; whereas, in animals, methazolamide does not impair diaphragm function. Compared with both methazolamide and the placebo, acetazolamide significantly compromised dorsiflexor function at rest and after exhaustive exercise. Similarly, diaphragm function was most compromised on acetazolamide followed by methazolamide and placebo. Methazolamide may be preferable over acetazolamide for clinical use and altitude illness prophylaxis to avoid skeletal muscle dysfunction.


Subject(s)
Acetazolamide/pharmacology , Carbonic Anhydrase Inhibitors/pharmacology , Methazolamide/pharmacology , Muscle Fatigue/drug effects , Respiratory Muscles/drug effects , Adult , Diaphragm/drug effects , Electric Stimulation , Electromyography , Exercise , Healthy Volunteers , Humans , Male , Muscle Contraction , Young Adult
19.
Physiother Theory Pract ; 34(4): 329-335, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29125380

ABSTRACT

Breathing retraining (BR) improves symptoms, psychological well-being and quality of life in adults with asthma; but there remains uncertainty as to mechanism of effect. One of the intuitively logical theories is that BR works through altering breathing pattern. There is currently no evidence, however, that BR does result in measurable changes in breathing pattern. In this case report we describe the effects of physiotherapy BR on a 57-year-old female with a 10-year history of asthma. Data were collected before and after a physiotherapy BR program comprising three sessions over 18 weeks: breathing pattern (respiratory inductive plethysmography (RIP); physiology (end tidal carbon dioxide (ETCO2), heart rate, oxygen saturations, spirometric lung function); questionnaires (Asthma Control Questionnaire (ACQ), Hospital Anxiety and Depression Score, Nijmegen Questionnaire); and medication usage. After BR, the patient's symptoms improved. Her physiology was largely unchanged, although her FEV1 increased by 0.12L, peak flow by 21L/min. The patient reported using less Salbutamol, yet her asthma control improved (ACQ down 1.5). Her Nijmegen score dropped from positive to negative for hyperventilation (from 39 to 7). Her anxiety-depression levels both reduced into 'normal' ranges. The patient's expiratory time increased, with longer respiratory cycles and slower respiratory rate. No changes were seen in relative contributions of ribcage and abdomen. Controlled trials are now needed to determine the generalizability of these findings.


Subject(s)
Asthma/therapy , Breathing Exercises , Lung/physiopathology , Plethysmography , Respiratory Mechanics , Respiratory Muscles/physiopathology , Albuterol/administration & dosage , Anxiety/psychology , Asthma/diagnosis , Asthma/physiopathology , Asthma/psychology , Bronchodilator Agents/administration & dosage , Depression/psychology , Female , Forced Expiratory Volume , Health Status , Humans , Lung/drug effects , Mental Health , Middle Aged , Respiratory Mechanics/drug effects , Respiratory Muscles/drug effects , Treatment Outcome
20.
Expert Rev Respir Med ; 12(1): 67-79, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29072087

ABSTRACT

INTRODUCTION: Respiratory muscle dysfunction is common and contributes to dyspnea and exercise limitation in patients with chronic obstructive pulmonary disease (COPD). Improving dynamic function of respiratory muscles during exercise might help to reduce symptoms and improve exercise capacity. Areas covered: The aims of this review are to 1) summarize physiological mechanisms linking respiratory muscle dysfunction to dyspnea and exercise limitation; 2) provide an overview of available therapeutic approaches to better maintain load-capacity balance of respiratory muscles during exercise; and 3) to summarize current knowledge on potential mechanisms explaining effects of interventions aimed at optimizing dynamic respiratory muscle function with a special focus on inspiratory muscle training. Expert commentary: Several mechanisms which are potentially linking improvements in dynamic respiratory muscle function to symptomatic and functional benefits have not been studied so far in COPD patients. Examples of underexplored areas include the study of neural processes related to the relief of acute dyspnea and the competition between respiratory and peripheral muscles for limited energy supplies during exercise. Novel methodologies are available to non-invasively study these mechanisms. Better insights into the consequences of dynamic respiratory muscle dysfunction will hopefully contribute to further refine and individualize therapeutic approaches in patients with COPD.


Subject(s)
Exercise Tolerance , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Muscles/physiopathology , Dyspnea/etiology , Dyspnea/physiopathology , Humans , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Respiratory Muscles/drug effects
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