ABSTRACT
BACKGROUND: Inherited mutations in SERPINA1 coding for the alpha-1 antitrypsin (A1AT) protein is the only well established cause of hereditary emphysema. We aimed to identify the genetic ecause of early-onset emphysema in a five-generation French-Canadian family free of A1AT deficiency. METHODS: Between Dec 1, 2014, and April 1, 2017, we investigated 63 individuals from a single pedigree, including 55 with DNA available. Whole-exome sequencing was done in a convenience sample of 14 individuals (nine with unambiguous expression of the typical form of emphysema observed in this family). We filtered rare non-synonymous variants that were predicted to be damaging to identify a single mutation in a biologically relevant gene shared among all affected individuals. We assessed segregation with the disease in additional family members who were not evaluated by whole-exome sequencing. The effect of the candidate variant on protein function was evaluated in vitro. mRNA and protein expression of the candidate gene was assessed in lung samples from unrelated individuals (n=80) with and without emphysema who underwent surgery for lung cancer at our institution. FINDINGS: A rare in-silico-predicted damaging variant (Ala455Thr) was identified in the protein tyrosine phosphatase non-receptor type 6 (PTPN6) gene, also known as SHP-1, an important negative regulator of immune processes. 20 (95%) of 21 family members with computed tomography-confirmed emphysema were heterozygotes for the Ala455Thr mutation. No Thr455 homozygotes were identified. Emphysema or reduced diffusion capacity was observed in all heterozygotes with a history of smoking. Incomplete penetrance of the mutation and variable degrees of emphysema were observed in never smokers. The Ala455Thr mutation in SHP-1 caused a reduction in phosphatase activity in vitro, confirming the loss-of-function effect of the mutation. mRNA and protein expression of PTPN6 were upregulated in smokers, but were not associated with emphysema or severity of airflow limitation. INTERPRETATION: An inherited variant in the gene PTPN6 is responsible for early-onset emphysema in this family. To our knowledge, this is the second form of hereditary emphysema since the discovery of A1AT deficiency in the 1960s, representing a breakthrough in understanding the genetics and pathogenesis of emphysema. FUNDING: Fonds sur les maladies respiratoires J.-D. Bégin-P.-H. Lavoie de l'Université Laval, Fondation de l'Institut universitaire de cardiologie et de pneumologie de Québec, CIHR/GSK research Chair on COPD at Université Laval, and the Canadian Institutes of Health Research.
Subject(s)
Genetic Predisposition to Disease/genetics , Mutation/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics , Pulmonary Emphysema/genetics , Adult , Aged , Aged, 80 and over , Canada , Female , Humans , Male , Middle Aged , Sequence Analysis, DNA , White PeopleSubject(s)
Dyspnea , Morphine , Forced Expiratory Volume , Humans , Pulmonary Disease, Chronic ObstructiveABSTRACT
Dyspnea is associated with an emotional reaction that involves limbic activation. The inspiratory threshold load (ITL) is known to elicit a dyspneic response in healthy subjects. Laboratory-induced stress conditions have been shown to elicit sex-related differences in cardiovascular responses. The aim of this study was to evaluate how healthy men (n = 8) and women (n = 9) react and adapt to 5-min periods of ITL at three levels (low, medium, and high) in terms of heart rate (HR), temporal (RMSSD) and spectral (LF, HF, LF/HF ratio) HRV indexes, and rating of breathing discomfort. HR increased with low, medium, and high ITL in men, whereas it increased only with high ITL in women. LF/HF ratio increased at low ITL in both men and women. Modifications appear to depend essentially on increased LF in men and on reduced HF in women. In addition, HRV modifications differ between men and women, following the order of presentation of ITLs. Our results show a continuous and sustained stress in men (increased HR, LF, and LF/HF ratio across ITL presentation) and a stress adaptation in women. Subjective responses of breathing discomfort were not correlated with sympatho-vagal balance modifications for a subgroup of subjects (n = 10). Breathing against the ITL induced autonomic modifications that are different between men and women, i.e., driven by sympathetic mediated responses in men, whereas women showed a greater parasympathetic modulation of cardiovascular activity. These results highlight the role of the mechanical inspiratory load in the heart rate variability seen in chronic obstructive pulmonary disease.NEW & NOTEWORTHY Breathing against the ITL induced autonomic modifications driven by sympathetic mediated responses in men, whereas women showed a greater parasympathetic modulation of cardiovascular activity, even for low load. A stress circuit could be at the origin of autonomic modifications induced by ITL. Our results would underline the role of the mechanic inspiratory load in the abnormalities in heart rate variability seen in COPD patients.
Subject(s)
Dyspnea/physiopathology , Heart Rate/physiology , Inhalation/physiology , Sex Characteristics , Stress, Psychological/physiopathology , Adult , Dyspnea/psychology , Female , Healthy Volunteers , Humans , Male , Random Allocation , Respiratory Function Tests/methods , Stress, Psychological/psychology , Young AdultABSTRACT
BACKGROUND: Dyspnoea is a threatening sensation of respiratory discomfort that presents many similarities with pain. Experimental dyspnoea in healthy subjects induces analgesia. This 'dyspnoea-pain counter-irritation' could, in reverse, imply that relieving dyspnoea in patients with chronic respiratory diseases would lower their pain thresholds. METHODS: We first determined pressure pain thresholds in 25 healthy volunteers (22-31â years; 13 men; handheld algometer), during unloaded breathing (BASELINE) and during inspiratory threshold loading (ITL). Two levels of loading were used, adjusted to induce dyspnoea self-rated at 60% or 80% of a 10â cm visual analogue scale (ITL6 and ITL8). 18 patients with chronic respiratory failure due to amyotrophic lateral sclerosis (ALS) were then studied during unassisted breathing and after 30 and 60â min of non-invasive ventilation-NIV30 and NIV60-(same dyspnoea evaluation). RESULTS: In healthy volunteers, pressure pain thresholds increased significantly in the deltoid during ITL6 (p<0.05) and ITL8 (p<0.05) and in the trapezius during ITL8 (p<0.05), validating the use of pressure pain thresholds to study dyspnoea-pain counter-irritation. In patients with ALS, the pressure pain thresholds measured in the deltoid during unassisted breathing decreased by a median of 24.5%-33.0% of baseline during NIV30 and NIV60 (p<0.05). CONCLUSION: Relieving dyspnoea by NIV in patients with ALS having respiratory failure is associated with decreased pressure pain thresholds. Clinical implications have yet to be determined, but this observation suggests that patients with ALS could become more susceptible to pain after the institution of NIV, hence the need for reinforced attention towards potentially painful diagnostic and therapeutic interventions.
Subject(s)
Amyotrophic Lateral Sclerosis/physiopathology , Dyspnea/prevention & control , Dyspnea/physiopathology , Noninvasive Ventilation , Pain Threshold , Adult , Aged , Female , France , Humans , Male , Middle Aged , Pain Management , Pain MeasurementABSTRACT
BACKGROUND: Dyspnoea is a distressing and debilitating symptom with a major impact on quality of life. Alleviation of dyspnoea therefore constitutes a major clinical challenge. When causative physiological disorders cannot be corrected ("persistent dyspnoea"), nonspecific treatment must be considered. Morphine alleviates dyspnoea but has numerous side-effects including ventilatory depression, which justifies looking for alternatives. Certain forms of dyspnoea involve C-fibres, and can be attenuated by C-fibres blockade. We hypothesised that nefopam, a non-sedative benzoxazocine analgesic known to block the transient receptor potential vanilloid subtype 1 abundantly present on C-fibres, would attenuate dyspnoea. METHODS: We conducted a randomised, double-blind, placebo-controlled crossover study of nefopam in healthy subjects submitted to experimental work/effort dyspnoea by inspiratory threshold loading (15 healthy male volunteers; age 23-41). We studied a perceptual outcome (dyspnoea visual analogue scale -D-VAS-) and a neurophysiological outcome (effect of nefopam on dyspnoea-pain counter-irritation as assessed by laser-evoked potentials; an effect of nefopam on dyspnoea was hypothetised to reduce the ability of dyspnoea to inhibit pain). Somaesthetic evoked potentials (SEPs) were studied as a control. RESULTS: A statistically significant decrease in LEP amplitude was observed in response to loading with nefopam (F = 19.1; p < 0.001) and placebo (F = 5.73 and p < 0.001), with no significant difference between nefopam and placebo and no change in SEP characteristics. CONCLUSIONS: In this study, nefopam did not exhibit any effects on dyspnoea.
Subject(s)
Analgesics, Non-Narcotic/pharmacology , Dyspnea/drug therapy , Nefopam/pharmacology , Adult , Cross-Over Studies , Double-Blind Method , Dyspnea/etiology , Evoked Potentials , Humans , Inspiratory Capacity/physiology , Male , Quality of Life , Visual Analog Scale , Young AdultABSTRACT
Dyspnea and pain share several characteristics and certain neural networks and interact with each other. Dyspnea-pain counter-irritation consists of attenuation of preexisting pain by intercurrent dyspnea and has been shown to have neurophysiological correlates in the form of inhibition of the nociceptive spinal reflex RIII and laser-evoked potentials (LEPs). Experimentally induced exertional dyspnea inhibits RIII and LEPs, while "air hunger" dyspnea does not inhibit RIII despite its documented analgesic effects. We hypothesized that air hunger may act centrally and inhibit LEPs. LEPs were obtained in 12 healthy volunteers (age: 21-29) during spontaneous breathing (FB), ventilator-controlled breathing (VC) tailored to FB, after inducing air hunger by increasing the inspired fraction of carbon dioxide -FiCO2- (VCCO2), and during ventilator-controlled breathing recovery (VCR). VCCO2 induced intense dyspnea (visual analog scale = 63% ± 6% of full scale, p < 0.001 vs. VC), predominantly of the air hunger type. VC alone reduced the amplitude of the N2-P2 component of LEPs (Δ = 24.0% ± 21.1%, p < 0.05, effect-size = 0.74) predominantly through a reduction in P2, and the amplitude of this inhibition was further reduced by inducting air hunger (Δ = 22.6% ± 17.9%, p < 0.05, effect-size = 0.53), predominantly through a reduction in N2. Somatosensory-evoked potentials (SEPs) were not affected by VC or VCCO2, suggesting that the observed effects are specific to pain transmission. We conclude that air hunger interferes with the cortical mechanisms responsible for the cortical response to painful laser skin stimulation, which provides a neurophysiological substrate to the central nature of its otherwise documented analgesic effects.
ABSTRACT
In awake humans, breathing depends on automatic brainstem pattern generators. It is also heavily influenced by cortical networks. For example, functional magnetic resonance imaging and electroencephalographic data show that the supplementary motor area becomes active when breathing is made difficult by inspiratory mechanical loads like resistances or threshold valves, which is associated with perceived respiratory discomfort. We hypothesized that manipulating the excitability of the supplementary motor area with repetitive transcranial magnetic stimulation would modify the breathing pattern response to an experimental inspiratory load and possibly respiratory discomfort. Seven subjects (three men, age 25 ± 4) were studied. Breathing pattern and respiratory discomfort during inspiratory loading were described before and after conditioning the supplementary motor area with repetitive stimulation, using an excitatory paradigm (5 Hz stimulation), an inhibitory paradigm, or sham stimulation. No significant change in breathing pattern during loading was observed after sham conditioning. Excitatory conditioning shortened inspiratory time (p = 0.001), decreased tidal volume (p = 0.016), and decreased ventilation (p = 0.003), as corroborated by an increased end-tidal expired carbon dioxide (p = 0.013). Inhibitory conditioning did not affect ventilation, but lengthened expiratory time (p = 0.031). Respiratory discomfort was mild under baseline conditions, and unchanged after conditioning of the supplementary motor area. This is the first study to show that repetitive transcranial magnetic stimulation conditioning of the cerebral cortex can alter breathing pattern. A 5 Hz conditioning protocol, known to enhance corticophrenic excitability, can reduce the amount of hyperventilation induced by inspiratory threshold loading. Further studies are needed to determine whether and under what circumstances rTMS can have an effect on dyspnoea.
ABSTRACT
In normal humans during quiet breathing, expiration is mostly driven by elastic recoil of the lungs. Expiration becomes active when ventilation must be increased to meet augmented metabolic demands, or in response to expiratory loading, be it experimental or disease-related. The response to expiratory loading is considered to be mediated by both reflex and cortical mechanisms, but the latter phenomenon have not been neurophysiologically characterized. We recorded the EEG in 20 healthy volunteers (9 men, 11 women, age: 22 to 50 yr) during unloaded breathing, voluntary expirations, and in response to 50 cmH2O·l(-1)·s expiratory resistive load (ERL), 20 cmH2O expiratory threshold load (high ETL), and 10 cmH2O expiratory threshold load (low ETL). EEGs were processed by ensemble averaging expiratory time-locked segments and examined for pre-expiratory potentials, defined as a slow negative shift from the baseline signal preceding expiration, and suggestive of cortical preparation of expiration involving the supplementary motor area. Four subjects were excluded because of technical EEG problems. Pre-expiratory potentials were present in one subject at baseline and in all subjects during voluntary expirations. They were present in eight subjects during low ETL, in 15 subjects during high ETL, and in 13 subjets during ERL (control vs. low ETL, P = 0.008; control vs. high ETL, P < 0.001; and control vs. ERL, P < 0.001). Respiratory discomfort was more intense in the presence of pre-expiratory potentials (P < 0.001). These results provide a neurophysiological substrate to a cortical component of the physiological response to experimental expiratory loads in humans.
Subject(s)
Electroencephalography , Exhalation , Motor Cortex/physiology , Adult , Female , Healthy Volunteers , Humans , Male , Membrane Potentials , Middle Aged , Random Allocation , Young AdultABSTRACT
Thoracoabdominal breathing movements are a complex source of postural disturbance, but there are contradictory reports in the literature with inspiration described as having either a backward or a forward disturbing effect. To elucidate the mechanisms underlying this phenomenon, the present study studied the postural disturbance caused by isolated contractions of the diaphragm. Eight male and four female healthy subjects followed an original paradigm of phrenic nerve stimulation (bilateral and unilateral) and "diaphragmatic" voluntary sniff maneuvers in the seated and standing postures. Center of gravity (CG) acceleration was calculated from force plate recordings, and respiratory kinematics were assessed with thoracic and abdominal sensor belts. CG and respiratory signals revealed that, while seated, bilateral phrenic stimulation and sniff maneuvers consistently produced expansion of the abdomen associated with a forward peak of CG acceleration. In the standing posture, the direction of the CG peak was reversed and always directed backward. Unilateral phrenic stimulation induced an additional medial-lateral acceleration of the CG, directed toward the nonactive side while seated, but in the opposite direction while standing. These results suggest that isolated diaphragmatic contractions produce a constant disturbing pattern for a given posture, but with opposite effects between standing and seated postures. This could be related to the different biomechanical configuration of the body in each posture, corresponding to distinct kinematic patterns of the osteoarticular chain. In addition, the lateral component of the CG acceleration induced by unilateral diaphragm contractions could be clinically relevant in patients with hemidiaphragm paralysis.
Subject(s)
Diaphragm/physiology , Muscle Contraction/physiology , Phrenic Nerve/physiology , Posture/physiology , Acceleration , Adult , Biomechanical Phenomena/physiology , Electric Stimulation/methods , Female , Gravitation , Humans , Male , Movement/physiology , RespirationABSTRACT
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible. In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease. Development of hyperinflation during the course of COPD is insidious. Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation. Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease. Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD. The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD. We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease.
Subject(s)
Lung/physiopathology , Pulmonary Disease, Chronic Obstructive/physiopathology , Animals , Comorbidity , Elasticity , Female , Humans , Lung Compliance , Lung Volume Measurements , Male , Predictive Value of Tests , Pressure , Prognosis , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/etiology , Risk Factors , Severity of Illness Index , Sex FactorsABSTRACT
Dyspnoea is a debilitating symptom that affects quality of life, exercise tolerance and mortality in various disease conditions/states. In patients with chronic obstructive pulmonary disease (COPD), it has been shown to be a better predictor of mortality than forced expiratory volume in 1 s. In patients with heart disease it is a better predictor of mortality than angina. Dyspnoea is also associated with decreased functional status and worse psychological health in older individuals living at home. It also contributes to the low adherence to exercise training programmes in sedentary adults and in COPD patients. The mechanisms of dyspnoea are still unclear. Recent studies have emphasised the multidimensional nature of dyspnoea in the sensory-perceptual (intensity and quality), affective distress and impact domains. The perception of dyspnoea involves a complex chain of events that depend on varying cortical integration of several afferent/efferent signals and coloured by affective processing. This review, which stems from the European Respiratory Society research symposium held in Paris, France in November 2012, aims to provide state-of-the-art advances on the multidimensional and multidisciplinary aspects of dyspnoea, by addressing three different themes: 1) the neurophysiology of dyspnoea, 2) exercise and dyspnoea, and 3) the clinical impact and management of dyspnoea.
Subject(s)
Dyspnea/diagnosis , Dyspnea/therapy , Pulmonary Medicine/methods , Congresses as Topic , Exercise , Exercise Tolerance , France , Health Status , Humans , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiration , Treatment OutcomeABSTRACT
INTRODUCTION: In humans, cortical mechanisms can interfere with autonomic breathing. Respiratory-related activation of the supplementary motor area (SMA) has been documented during voluntary breathing and in response to inspiratory constraints. The SMA could therefore participate in the increased resting state of the respiratory motor system during wake (i.e. "wakefulness drive to breathe"). METHODS: The SMA was conditioned by continuous theta burst magnetic stimulation (cTBS, inhibitory) and 5 Hz conventional rTMS (5 Hz, excitatory). The ensuing effects were described in terms of the diaphragm motor evoked response (DiMEPs) to single-pulse transcranial magnetic stimulation over the motor cortex. DiMEPs were recorded at baseline, and at 3 time-points ("post1", "post2", "post3") up to 15 minutes following conditioning of the SMA. RESULTS: cTBS reduced the amplitude of DiMEPs from 327.5 ± 159.8 µV at baseline to 243.3 ± 118.7 µV, 217.8 ± 102.9 µV and 240.6 ± 123.9 µV at post 1, post 2 and post 3, respectively (Fâ=â6.341, pâ=â0.002). 5 Hz conditioning increased the amplitude of DiMEPs from 184.7 ± 96.5 µV at baseline to 270.7 ± 135.4 µV at post 3 (Fâ=â4.844, pâ=â0.009). CONCLUSIONS: The corticospinal pathway to the diaphragm can be modulated in both directions by conditioning the SMA. This suggests that the baseline respiratory activity of the SMA represents an equipoise from which it is possible to move in either direction. The resting corticofugal outflow from the SMA to phrenic motoneurones that this study evidences could putatively contribute to the wakefulness drive to breathe.
Subject(s)
Motor Cortex/physiology , Motor Neurons/metabolism , Evoked Potentials, Motor/physiology , Humans , Motor Neurons/cytology , Transcranial Magnetic Stimulation , Wakefulness/physiologyABSTRACT
Patients with pulmonary arterial hypertension (PAH) may exhibit reduced expiratory flows at low lung volumes, which could promote exercise-induced dynamic hyperinflation (DH). This study aimed to examine the impact of a potential exercise-related DH on the intensity of dyspnoea in patients with PAH undergoing symptom-limited incremental cardiopulmonary cycle exercise testing (CPET). 25 young (aged mean±sd 38±12 yrs) nonsmoking PAH patients with no evidence of spirometric obstruction and 10 age-matched nonsmoking healthy subjects performed CPET to the limit of tolerance. Ventilatory pattern, operating lung volumes (derived from inspiratory capacity (IC) measurements) and dyspnoea intensity (Borg scale) were assessed throughout CPET. IC decreased (i.e. DH) progressively throughout CPET in PAH patients (average 0.15 L), whereas it increased in all the healthy subjects (0.45 L). Among PAH patients, 15 (60%) exhibited a decrease in IC throughout exercise (average 0.50 L), whereas in the remaining 10 (40%) patients IC increased (average 0.36 L). Dyspnoea intensity and ventilation were greater in PAH patients than in controls at any stage of CPET, whereas inspiratory reserve volume was lower. We conclude that DH-induced mechanical constraints and excessive ventilatory demand occurred in these young nonsmoking PAH patients with no spirometric obstruction and was associated with exertional dyspnoea.
Subject(s)
Dyspnea/complications , Hypertension, Pulmonary/physiopathology , Respiratory Mechanics , Adult , Case-Control Studies , Dyspnea/physiopathology , Exercise , Exercise Test , Familial Primary Pulmonary Hypertension , Female , Forced Expiratory Volume , Humans , Hypertension, Pulmonary/diagnosis , Inspiratory Capacity , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND: experimentally induced dyspnea of the work/effort type inhibits, in a top-down manner, the spinal transmission of nociceptive inputs (dyspnea-pain counterirritation). Previous studies have demonstrated that this inhibition can be assessed by measuring the nociceptive flexion reflex (RIII). However, its clinical application is limited because of the strong discomfort associated with the electrical stimuli required to elicit the RIII reflex. STUDY OBJECTIVES: we examined whether the dyspnea-pain counterirritation phenomenon can be evaluated by measuring the effect of work/effort type dyspnea on the magnitude of laser-evoked brain potentials (LEPs). METHODS: 10 normal male volunteers were studied (age: 19-30 years). LEPs were elicited using a CO(2) laser stimulator delivering 10- to 15-ms stimuli of 6 ± 0.7 W over a 12.5 mm(2) area. The EEG was recorded using nine scalp channels. Non-nociceptive somatosensory-evoked potentials (SEPs) served as control. LEPs and SEPs were recorded before, during, and after 10 min of experimentally induced dyspnea [inspiratory threshold loading (ITL)]. RESULTS: pain caused by the nociceptive laser stimulus was mild. ITL consistently induced dyspnea, mostly of the "excessive effort" type. Amplitude of the N2-P2 wave of LEPs decreased by 37.6 ± 13.8% during ITL and was significantly correlated with the intensity of dyspnea [r = 0.66, CI 95% (0.08-0.92, P = 0.0319)]. In contrast, ITL had no effect on the magnitude of non-nociceptive SEPs. DISCUSSION: experimentally induced dyspnea of the work/effort type reduces the magnitude of LEPs. This reduction correlates with the intensity of dyspnea. The recording of LEPs could constitute a clinically applicable approach to assess the dyspnea-pain counterirritation phenomenon in patients.
Subject(s)
Dyspnea/therapy , Evoked Potentials/physiology , Laser Therapy , Pain Management/methods , Adult , Dyspnea/complications , Electroencephalography , Evoked Potentials, Somatosensory/physiology , Humans , Male , Nerve Fibers, Myelinated/physiology , Nerve Fibers, Unmyelinated/physiology , Pain/etiology , Pain Measurement , Physical Exertion/physiology , Respiratory Mechanics/physiology , Signal Processing, Computer-Assisted , Young AdultABSTRACT
RATIONALE: The endurance time (T(end)) during constant-workrate cycling exercise (CET) is highly variable in COPD. We investigated pulmonary and physiological variables that may contribute to these variations in T(end). METHODS: Ninety-two patients with COPD completed a CET performed at 80% of peak workrate capacity (W(peak)). Patients were divided into tertiles of T(end) [Group 1: <4 min; Group 2: 4-6 min; Group 3: >6 min]. Disease severity (FEV(1)), aerobic fitness (W(peak), peak oxygen consumption [VO2(peak)], ventilatory threshold [VO2(VT)]), quadriceps strength (MVC), symptom scores at the end of CET and exercise intensity during CET (heart rate at the end of CET to heart rate at peak incremental exercise ratio [HR(CET)/HR(peak)]) were analyzed as potential variables influencing T(end). RESULTS: W(peak), VO2(peak), VO2(VT), MVC, leg fatigue at end of CET, and HR(CET)/HR(peak) were lower in group 1 than in group 2 or 3 (p≤0.05). VO2(VT) and leg fatigue at end of CET independently predicted T(end) in multiple regression analysis (râ=â0.50, pâ=â0.001). CONCLUSION: T(end) was independently related to the aerobic fitness and to tolerance to leg fatigue at the end of exercise. A large fraction of the variability in T(end) was not explained by the physiological parameters assessed in the present study. Individualization of exercise intensity during CET should help in reducing variations in T(end) among patients with COPD.
Subject(s)
Bicycling/physiology , Exercise Test/methods , Exercise/physiology , Physical Endurance/physiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Aged , Exercise Tolerance/physiology , Female , Heart Rate/physiology , Humans , Individuality , Male , Middle Aged , Oxygen Consumption/physiology , Respiratory Function Tests , Time FactorsABSTRACT
BACKGROUND: The endurance shuttle walking test (ESWT) has shown good responsiveness to interventions in patients with chronic obstructive pulmonary disease (COPD). However, the minimal important difference (MID) for this test remains unknown, therefore limiting its interpretability. METHODS: Patients with COPD who completed two or more ESWTs following pulmonary rehabilitation (n=132; forced expiratory volume in 1 s (FEV1) 48 ± 22%) or bronchodilation (n=69; FEV1 50 ± 12%) rated their performance of the day in comparison with their previous performance on a 7-point scale ranging from -3 (large deterioration) to +3 (large improvement). The relationship between subjective perception of changes and objective changes in performance during the shuttle walk was evaluated. RESULTS: Following pulmonary rehabilitation, the anchor-based approach did not allow a valid estimation of the MID in the ESWT performance to be obtained. After bronchodilation, patient ratings of change correlated significantly with the difference in walking distance (r=0.53, p<0.001) and endurance time (r=0.55, p<0.001). For the pharmacotherapy data, regression analysis indicated that a 65 s (95% CI 45 to 85) change in endurance time and a 95 m (95% CI 60 to 115) change in walking distance were associated with a 1-point change in the rating of change scale. These changes represented 13-15% of the baseline values. CONCLUSIONS: A change in endurance shuttle walking performance of 45-85 s (or 60-115 m) after bronchodilation is likely to be perceived by patients. This MID value may be specific to the intervention from which it was derived.
Subject(s)
Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/rehabilitation , Walking/physiology , Adult , Aged , Aged, 80 and over , Attitude to Health , Bronchodilator Agents/therapeutic use , Epidemiologic Methods , Exercise Test/methods , Exercise Therapy/methods , Exercise Tolerance/physiology , Female , Forced Expiratory Volume/physiology , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/drug therapy , Treatment Outcome , Vital Capacity/physiologyABSTRACT
BACKGROUND: We examined the influence of overweight and obesity on pulmonary function, exercise tolerance, quality of life and response to pulmonary rehabilitation in COPD. METHODS: 261 patients with COPD were divided into three groups: normal body mass index (BMI), overweight and obese. Baseline and post rehabilitation pulmonary function, 6-min walking test (6MWT), endurance time during a constant workrate exercise test (CET) and St. George's Respiratory Questionnaire (SGRQ) scores were compared between all three classes of BMI. RESULTS: At baseline, obese and overweight patients had less severe airflow obstruction compared to normal BMI patients. There was no baseline difference in CET performance or SGRQ scores across BMI classes and 6MWT was reduced in the presence of obesity (p < 0.01). Compared to baseline, post-rehabilitation 6MWT, CET performance and SGRQ scores improved significantly in each group (p < 0.01), but 6MWT was still significantly lower in the presence of obesity. CONCLUSIONS: Walking, but not cycling performance was worse in obese patients. This difference was maintained post rehabilitation despite significant improvements. Weight excess may counterbalance the effect of a better preserved respiratory function in the performance of daily activities such as walking. However, obesity and overweight did not influence the magnitude of improvement after pulmonary rehabilitation.
Subject(s)
Obesity/physiopathology , Overweight/physiopathology , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/rehabilitation , Aged , Body Mass Index , Dyspnea/complications , Dyspnea/physiopathology , Ergometry , Exercise Test , Exercise Tolerance/physiology , Female , Humans , Lung Volume Measurements , Male , Middle Aged , Obesity/complications , Physical Exertion/physiology , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Ventilation/physiology , Quality of Life , Spirometry , Treatment Outcome , Walking/physiologyABSTRACT
Pressurized whey supplementation, by its antioxidant and nutritional properties, may improve exercise tolerance and potentiate the effects of exercise training in patients with chronic obstructive pulmonary disease (COPD). In this randomized, double-blind, placebo-controlled study, 22 patients with COPD were allocated to receive active pressurized whey or placebo (casein) dietary supplementation for a 16-week period. Patients continued their usual physical activities for the first 8 weeks, whereas they were subjected to an exercise training program for the remaining 8 weeks of the study. Patients were evaluated at baseline, after 8 weeks of supplementation alone (time point, 8 weeks), and after 8 weeks of its combination with exercise training (time point, 16 weeks). The constant workrate cycle endurance test (CET), potentiated quadriceps twitch force, mid-thigh cross-sectional area, and Chronic Respiratory Questionnaire (CRQ) were used to evaluate the effects of treatments. The inflammatory (C-reactive protein and interleukin-6) and oxidant/antioxidant (protein oxidation and glutathione) blood profiles were also characterized. At week 8, there was no increase in CET time in either group. At week 16, there was a statistically significant increase in CET time in the whey-only group (P < .05). Further, at week 16, there was clinically significant improvement in the Dyspnea and the Mastery scales of the CRQ in both groups. Also, the Fatigue and Emotional Control scales of the CRQ showed clinically significant improvement in the whey-only group. Study interventions did not modify significantly the systemic inflammatory and oxidative stress markers that were assessed. Thus dietary supplementation with pressurized whey may potentiate the effects of exercise training on exercise tolerance and quality of life in patients with COPD.