Thoraco-abdominal motion/displacement does not affect dyspnea following exercise training in COPD patients.

PURPOSE: The interrelations among chest wall kinematics (displacement and configuration), ventilatory profile and dyspnea relief following cycle exercise training (EXT) have not been systematically evaluated in hyperinflated chronic obstructive pulmonary disease (COPD) patients. We hypothesize that a decrease in ventilation affects dyspnea relief, regardless of the changes in chest wall kinematics. METHODS: Fourteen patients were studied before and after 24-session exercise training program. We evaluated the volumes of chest wall and its compartments (rib cage, and abdomen) using optoelectronic plethysmography. RESULTS: At iso-time EXT (i) reduced ventilation, respiratory frequency and dyspnea (by Borg scale), mildly improved rib cage configuration, but left operational volumes unchanged; (ii) Borg was much smaller for any comparable inspiratory reserve volume (IRVcw), and a decrease in IRVcw was tolerated much better for any given Borg. CONCLUSIONS: Regardless of the changes in chest wall kinematics, a decrease in ventilation attenuates dyspnea following EXT.

Dyspnea and emotional states in health and disease.

Anxiety and depression can increase the intensity of dyspnea out of proportion to the impairment in cardiorespiratory function and may contribute to the degree of disability associated with dyspnea. The effect of anxiety/depression on the sensory and affective components of reported dyspnea in patients with respiratory disorders might be of particular importance in improving the accuracy of the diagnostic process. However, the exact cause-relationship between dyspnea and anxiety/depression are unclear. A multidimensional model of dyspnea subsuming sensory components (i.e. intensity and quality) and affective components has recently been proposed. Affective responses drive patients to seek treatment which can cause them to alter their lifestyle to avoid dyspnea. Brain imaging techniques help identify distinct cortical structures involved in processing the discrete components of dyspnea.

Tidal volume inflection and its sensory consequences during exercise in patients with stable asthma.

Sixteen patients with stable asthma performed a symptom-limited constant work-rate CWR cycle exercise during which breathing pattern, operating lung volumes, dyspnea intensity and its qualitative descriptors were measured. An inflection in the relation between tidal volume (V(T)) and ventilation (V˙(E)) was observed in each subject. The sense of "work/effort" was the dominant dyspnea descriptor selected up to the V(T)/V˙(E) inflection, whereas after it dyspnea intensity and the selection frequency of "unsatisfied inspiration" rose steeply in 37.5% of subjects in whom inspiratory reserve volume (IRV) had decreased to a critical level of 0.6L at the V(T) inflection point. In contrast, dyspnea increased linearly with exercise time and V˙(E), and "work/effort" was the dominant descriptor selected throughout exercise in 62.5% of subjects in whom the V(T)/V˙(E) inflection occurred at a preserved IRV. The V(T) inflection during exercise in patients with stable asthma marked a mechanical event with important sensory consequences only when it occurred at a critical reduced IRV.

Mechanical correlates of dyspnea in bronchial asthma.

We hypothesized that dyspnea and its descriptors, that is, chest tightness, inspiratory effort, unrewarded inspiration, and expiratory difficulty in asthma reflect different mechanisms of airflow obstruction and their perception varies with the severity of bronchoconstriction. Eighty-three asthmatics were studied before and after inhalation of methacholine doses decreasing the 1-sec forced expiratory volume by ~15% (mild bronchoconstriction) and ~25% (moderate bronchoconstriction). Symptoms were examined as a function of changes in lung mechanics. Dyspnea increased with the severity of obstruction, mostly because of inspiratory effort and chest tightness. At mild bronchoconstriction, multivariate analysis showed that dyspnea was related to the increase in inspiratory resistance at 5 Hz (R 5) (r (2) = 0.10, P = 0.004), chest tightness to the decrease in maximal flow at 40% of control forced vital capacity, and the increase in R 5 at full lung inflation (r (2) = 0.15, P = 0.006), inspiratory effort to the temporal variability in R 5-19 (r (2) = 0.13, P = 0.003), and unrewarded inspiration to the recovery of R 5 after deep breath (r (2) = 0.07, P = 0.01). At moderate bronchoconstriction, multivariate analysis showed that dyspnea and inspiratory effort were related to the increase in temporal variability in inspiratory reactance at 5 Hz (X 5) (r (2) = 0.12, P = 0.04 and r (2) = 0.18, P < 0.001, respectively), and unrewarded inspiration to the decrease in X 5 at maximum lung inflation (r (2) = 0.07, P = 0.04). We conclude that symptom perception is partly explained by indexes of airway narrowing and loss of bronchodilatation with deep breath at low levels of bronchoconstriction, but by markers of ventilation heterogeneity and lung volume recruitment when bronchoconstriction becomes more severe.

Obstructive sleep apnea (OSA) does not affect ventilatory and perceptual responses to exercise in morbidly obese subjects.

We have tested the hypothesis that high mass loading effects and obstructive sleep apnea (OSA) constrain the ventilatory response to exercise in morbidly obese subjects as compared to their counterparts without OSA. Fifteen obese patients with (8) and without OSA and 12 lean healthy subjects performed incremental cycle exercise. The functional evaluation included ventilation, oxygen uptake, carbon dioxide production, end-expiratory-lung-volumes (EELV), inspiratory capacity, heart rate, dyspnea and leg effort (by a modified Borg scale). Changes in ventilation and dyspnea per unit changes in work rate and metabolic variables were similar in the three groups. Breathing pattern and heart rate increased from rest to peak exercise similarly in the three groups. Leg effort was the prevailing symptom for stopping exercise in most subjects. In conclusion, OSA does not limit exercise capacity in morbidly obese subjects. Ventilation contributes to exertional dyspnea similarly as in lean subjects and in obese patients regardless of OSA.

Dyspnea, chest wall hyperinflation, and rib cage distortion in exercising patients with chronic obstructive pulmonary disease.

PURPOSE: Whether dyspnea, chest wall dynamic hyperinflation, and abnormalities of rib cage motion are interrelated phenomena has not been systematically evaluated in patients with chronic obstructive pulmonary disease (COPD). Our hypothesis that they are not interrelated was based on the following observations: (i) externally imposed expiratory flow limitation is associated with no rib cage distortion during strenuous incremental exercise, with indexes of hyperinflation not being correlated with dyspnea, and (ii) end-expiratory chest wall volume may either increase or decrease during exercise in patients with COPD, with those who hyperinflate being as breathless as those who do not. METHODS: Sixteen patients breathed either room air or 50% supplemental O2 at 75% of peak exercise in randomized order. We evaluated the volume of chest wall (V(cw)) and its compartments: the upper rib cage (V(rcp)), lower rib cage (V(rca)), and abdomen (V(ab)) using optoelectronic plethysmography; rib cage distortion was assessed by measuring the phase angle shift between V(rcp) and V(rca). RESULTS: Ten patients increased end-expiratory V(cw) (V(cw,ee)) on air. In seven hyperinflators and three non-hyperinflators, the lower rib cage paradoxed inward during inspiration with a phase angle of 63.4° ± 30.7° compared with a normal phase angle of 16.1° ± 2.3° recorded in patients without rib cage distortion. Dyspnea (by Borg scale) averaged 8.2 and 9 at the end of exercise on air in patients with and without rib cage distortion, respectively. At iso-time during exercise with oxygen, decreased dyspnea was associated with a decrease in ventilation regardless of whether patients distorted the rib cage, dynamically hyperinflated, or deflated the chest wall. CONCLUSIONS: Dyspnea, chest wall dynamic hyperinflation, and rib cage distortion are not interrelated phenomena.

Prevalence of limb muscle dysfunction in patients with chronic obstructive pulmonary disease admitted to a pulmonary rehabilitation centre.

OBJECTIVE: Assessment of needle electromyography (nEMG) may complement previous data on limb muscle dysfunction (LMD) in patients with chronic obstructive pulmonary disease (COPD). We attempted to quantify the prevalence of LMD and assess its impact on clinical outcomes in patients admitted to a rehabilitation programme. METHODS: One hundred and thirty-two clinically stable patients were consecutively enrolled. They underwent spirometry and the following primary outcomes were evaluated: St. George respiratory questionnaire (SGRQ), functional independence measure (FIM) questionnaire and a 6-min walking test (6MWT). One hundred and fourteen patients underwent nEMG. The frequency of LMD was related to COPD stage and chronic dyspnoea. RESULTS: nEMG detected myopathic signs in 36.8% of the patients. LMD was found even in early stages of COPD. FIM and 6MWT were significantly lower, and SGRQ tended to be higher at each COPD stage in patients with LMD. However, the 6MWT rate of decay across the COPD stages was similar in patients with and without LMD. CONCLUSIONS: LMD might not be restricted to patients with severe airway obstruction and regardless of COPD stage, contributes to functional limitation of these patients. SIGNIFICANCE: The putative role of LMD in motor limitations indicates the need to assess it early onto better organise a specific training programme as part of general pulmonary rehabilitation in COPD patients.

Chest wall kinematics and breathlessness during unsupported arm exercise in COPD patients.

We hypothesised that chest wall displacement inappropriate to increased ventilation contributes to dyspnoea more than dynamic hyperinflation or dyssynchronous breathing during unsupported arm exercise (UAE) in COPD patients. We used optoelectronic plethysmography to evaluate operational volumes of chest wall compartments, the upper rib cage, lower rib cage and abdomen, at 80% of peak incremental exercise in 13 patients. The phase shift between the volumes of upper and lower rib cage (RC) was taken as an index of RC distortion. With UAE, no chest wall dynamic hyperinflation was found; sometimes the lower RC paradoxed inward while in other patients it was the upper RC. Phase shift did not correlate with dyspnoea (by Borg scale) at any time, and chest wall displacement was in proportion to increased ventilation. In conclusions neither chest wall dynamic hyperinflation nor dyssynchronous breathing per se were major contributors to dyspnoea. Unlike our prediction, chest wall expansion and ventilation were adequately coupled with each other.

Formoterol by pressurized metered-dose aerosol or dry powder on airway obstruction and lung hyperinflation in partially reversible COPD.

BACKGROUND: We compared the efficacy and safety of formoterol given by a pressurized metered-dose inhaler (pMDI) (Atimos®, Chiesi Farmaceutici, Italy), using a chlorine-free hydrofluoroalkane (HFA-134a) propellant developed to provide stable and uniform dose delivery (Modulite™, Chiesi Farmaceutici, Italy), with formoterol by dry powder inhaler (DPI) (Foradil® Aerolizer®, Novartis Pharmaceuticals) and placebo, in reducing airflow obstruction and lung hyperinflation, in moderate-to-severe, partially reversible chronic obstructive pulmonary disease (COPD). METHODS: Forty-eight patients were randomized to a 1-week, double-blind, double-dummy, three-period crossover study with 12 µg b.i.d. of formoterol given by pMDI or DPI, or placebo. Spirometry, specific airway conductance, and lung volumes were measured at the beginning and at the end of each treatment period from predose to 4 h postdose. A 6-min walking test was carried out 4 h after the first and the last dose, with dyspnea assessed by Borg scale. Safety was assessed through adverse events monitoring electrocardiography and vital signs. RESULTS: The two formulations of formoterol were significantly superior to placebo but not different from each other in increasing 1-sec forced expiratory volume, specific airway conductance, inspiratory capacity, and inspiratory-to-total lung capacity ratio. The two active treatments were also equivalent and superior to placebo in reducing dyspnea at rest and on exertion. No differences in terms of safety between the two active forms and placebo were detected. CONCLUSIONS: Formoterol given with chlorine-free pMDI was equivalent to DPI in reducing airway obstruction and lung hyperinflation in COPD patients. Both formoterol formulations confirmed the good safety profile similar to placebo.

Dyspnea during speech in chronic obstructive pulmonary disease patients: effects of pulmonary rehabilitation.

BACKGROUND: For patients with limited physical activities who use oral communication for most social activities, the assessment of dyspnea during speech activities (DS) may provide relevant measurement criteria. Although speech production is altered by lung disease it has not been included in current dyspnea assessment tools. OBJECTIVES: We evaluated DS in patients with chronic obstructive pulmonary disease (COPD) with the aim of assessing: (i) the responsiveness to treatment of this newly developed evaluative dyspnea tool and (ii) whether DS is an independent measurement of other traditional outcomes. METHODS: We assessed lung function, the 6-min walking test (6'WT), chronic exertional dyspnea (MRC and BDI/TDI), and DS using the speech section of the University of Cincinnati Dyspnea Questionnaire (UCDQ) before and after a pulmonary rehabilitation program in 31 patients with COPD. RESULTS: The following items of the speech section of the UCDQ caused dyspnea: conversation, raising the voice, phoning, speaking to a group, talking in a noisy place, and singing. The mean overall DS score was 60 ± 23% of a maximal potential DS score. Pulmonary rehabilitation reduced each item of DS independently of change in lung function, chronic exertional dyspnea, and 6'WT. CONCLUSIONS: We concluded that DS is responsive to a respiratory rehabilitation program in patients with COPD. Evidence of independent objective measures supports the validity of a routine multivariable assessment including DS. We recommend assessment of DS particularly for patients who rely extensively on speech for communication.

Impact of a rehabilitation program on dyspnea intensity and quality in patients with chronic obstructive pulmonary disease.

BACKGROUND: It has yet to be determined whether the language of dyspnea responds to pulmonary rehabilitation programs (PRP). OBJECTIVE: We tested the hypothesis that PRP affect both the intensity and quality of exercise-induced dyspnea in patients with chronic obstructive pulmonary disease (COPD). METHODS: We studied 49 patients equipped with a portable telemetric spiroergometry device during the 6-min walking test before and 4 weeks after PRP. In a first screening visit, appropriate verbal descriptors of dyspnea were chosen that patients were familiar with during daily living activities. Tidal volume, respiratory frequency, inspiratory capacity, inspiratory reserve volume (IRV) and dyspnea intensity were evaluated by a modified Borg scale every minute during the test. RESULTS: Qualitative descriptors of dyspnea were defined by three different sets of cluster descriptors (a-c) at the end of the exercise test, before and after PRP: a - work/effort (W/E); b - inspiratory difficulty (ID) and chest tightness (CT), and c - W/E, ID and/or CT. The three language subgroups exhibited similar lung function at baseline, and similar rating of dyspnea and ventilatory changes during exercise. The rehabilitation program shifted the Borg-IRV relationship (less Borg at any given IRV) towards the right without modifying the set of descriptors in most patients. CONCLUSIONS: Rehabilitation programs allowed patients to tolerate a greater amount of restrictive dynamic ventilatory defect by modifying the intensity, but not necessarily the quality of dyspnea.

Effect of limb muscle fatigue on perception of respiratory effort in healthy subjects.

The role of nonrespiratory peripheral afferents in dyspnea perception has not been fully elucidated yet. Our hypothesis is that fatigue-induced activation of limb muscle metaboreceptors served by group IV fine afferent fibers may impact on respiratory effort perception. We studied 12 healthy subjects breathing against progressive inspiratory resistive loads (10, 18, 30, 40, and 90 cmH(2)O x l(-1) x s) before and after inducing low-frequency fatigue of quadriceps muscle by repeating sustained contractions at > or = 80% of maximal voluntary contraction. Subjects also underwent a sham protocol while performing two loaded breathing runs without muscle fatigue in between. During the loaded breathing, while subjects mimicked the quiet breathing pattern using a visual feedback, ventilation, tidal volume, respiratory frequency, pleural pressure swings, arterial oxygen saturation, end-tidal partial pressure of CO(2), and dyspnea by a Borg scale were recorded. Compared with prefatigue, limb muscle fatigue resulted in a higher increase in respiratory effort perception for any given ventilation, tidal volume, respiratory frequency, pleural pressure swings, end-tidal partial pressure of CO(2), and arterial oxygen saturation. No difference between the two runs was observed with the sham protocol. The present data support the hypothesis that fatigue of limb muscles increases respiratory effort perception associated with loaded breathing, likely by the activation of limb muscle metaboreceptors.

Do obstructive and restrictive lung diseases share common underlying mechanisms of breathlessness?

This review tries to answer two main questions: (i) What are the neurophysiological underpinnings of the most commonly selected cluster descriptors which define the qualitative dimension of dyspnea in patients? (ii) How do mechanical constraints affect dyspnea? (iii) Do obstructive and restrictive lung diseases share some common underlying mechanisms? Qualitative dimensions of dyspnea, which allude to increased respiratory work/effort breathing, reflect a harmonious coupling between increased respiratory motor output and lung volume displacement in healthy subjects. Descriptors that allude to unsatisfied inspiration are the dominant qualitative descriptors in patients with a variety of respiratory diseases. It is possible that sensory feedback from a multitude of mechanoreceptors throughout the respiratory system (in the muscle, chest wall, airways and lung parenchyma) collectively convey information to the consciousness that volume/flow or chest wall displacement is inadequate for the prevailing respiratory drive. The data would lend support to the idea that: (i) an altered afferent proprioceptive peripheral feedback signals that ventilatory response is inadequate to the prevailing motor drive, reflecting neuromechanical uncoupling (NMU), (ii) mechanical constraints on volume expansion (dynamic restriction) play a pivotal role in dyspnea causation in patients with a variety of either obstructive or restrictive respiratory disorders, and (iii) all of the physiological adaptations that optimize neuromechanical coupling in obstructive and restrictive disorders are seriously disrupted so that an NMU underpins cluster descriptors of dyspnea which are similar in obstructed and in restricted patients.

Airway hyperresponsiveness with chest strapping: A matter of heterogeneity or reduced lung volume?

Chest wall strapping has been recently shown to be associated with an increase in airway responsiveness to methacholine. To investigate whether this is the result of the decreased lung volume or an increased heterogeneity due to chest wall distortion, ten healthy volunteers underwent a methacholine challenge at control conditions and after selective strapping of the rib cage, the abdomen or the whole chest wall resulting in similar decrements of functional residual capacity and total lung capacity but causing different distribution of the bronchoconstrictor. Methacholine during strapping reduced forced expiratory flow, dynamic compliance, and reactance at 5Hz and increased pulmonary resistance and respiratory resistance at 5Hz that were significantly greater than at control and associated with a blunted bronchodilator effect of the deep breath. However, no significant differences were observed between selective and total chest wall strapping, suggesting that the major mechanism for increasing airway responsiveness with chest wall strapping is the breathing at low lung volume rather than regional heterogeneities.

The respiratory muscles in eucapnic obesity: their role in dyspnea.

Regular exercise appears to be one of the best predictors of successful weight maintenance. Although physical activity and exercise are important components in the prevention and treatment of obesity, many obese adults without coexisting disorders are unable to exercise due to dyspnea on exertion. As a result they may not participate in regular physical activity. Therefore exertional dyspnea in obese adults is also an obstacle to the prevention and treatment of obesity and coexisting comorbidities. The available data suggest that increased respiratory muscle force generation, and the concomitant increase in respiratory neural drive associated with increased ventilation are an important source of sensation of respiratory effort in obese subjects. Whether activity-related breathlessness is due to either abnormal respiratory mechanical factors (flow limitation and/or chest elastic loading) or the increased metabolic demand of locomotion in obesity, or both of these together, the available data indicate that intensity of dyspnea at any given ventilation and oxygen uptake does not increase in obese subjects as compared with normal weight control subjects. Does this mean that respiratory mechanical factors are unlikely to be contributory? Nonetheless, the component of metabolic cost of breathing may not be accounted for in the measured mechanical work of breathing because of the number of included complex variables. That a decrease in efficiency of the respiratory muscles during exercise contributes to dyspnea in hyperinflating obese subjects should not be disregarded.

Effect of biventricular pacing on ventilatory and perceptual responses to exercise in patients with stable chronic heart failure.

Despite the growing evidence supporting the use of biventricular cardiac resynchronization therapy (CRT) in patients with chronic heart failure (CHF), the mechanisms whereby acute hemodynamic improvements lead to improved exertional dyspnea are not precisely known. We hypothesized that improved cardiac function and ventilation-perfusion relations following CRT would reduce ventilatory demand, thereby improving dynamic operating lung volumes and enhancing tidal volume expansion during exercise. This, in turn, would be expected to reduce perceived exertional dyspnea and contribute to improved exercise performance. In a randomized, double-blind, crossover study, we compared cardiovascular, metabolic, ventilatory responses (breathing pattern, operating lung volumes, pulmonary gas exchange) and exertional symptoms in seven stable CHF patients who undertook incremental cardiopulmonary cycle exercise test with CRT switched to the "on" (CRT(on)) or "off" (CRT(off)) modality. Following CRT(on), peak oxygen uptake was significantly increased by 15%, and dyspnea ratings were lower for a given work rate (at work rate of 40 W, dyspnea = 1 +/- 0.4 vs. 2.5 +/- 0.9 Borg units, P < 0.05) and ventilation (at ventilation of 31 l/min, dyspnea = 2 +/- 0.7 vs. 3.3 +/- 1.1 Borg units, P < 0.05). CRT(on) was associated with improvements in ventilatory threshold, oxygen pulse, and oxygen uptake/work rate relationships (10.2 +/- 1 vs. 7.9 +/- 1.3 ml.min(-1).W(-1), P < 0.05). CRT(on) reduced the ventilatory requirement during exercise as well as the steepness of ventilation-CO(2) production slope (35 +/- 4 vs. 45 +/- 7, P < 0.05). Changes in end-expiratory lung volume during exercise were less with CRT(on) than with CRT(off) (0.12 vs. 0.37 liter, P < 0.05), and breathing pattern was correspondingly slower and deeper. Biventricular pacing improved all noninvasive indexes of cardiac function and oxygen delivery during exercise. The decreased ventilatory demand, improved dynamic operating lung volumes, and the increased ability to expand tidal volume during exercise are potential factors in the reduction of exertional dyspnea.

Chest wall kinematics during voluntary cough in neuromuscular patients.

Muscular diseases are characterized by progressive loss of muscle strength, resulting in cough ineffectiveness with its deleterious effects on the respiratory system. Assessment of cough effectiveness is therefore a prominent component of the clinical evaluation and respiratory care in these patients. Owing to uneven distribution of muscle weakness in neuromuscular patients, we hypothesized that forces acting on the chest wall may impact on the compartmental distribution of gas volume resulting in a decrease in cough effectiveness. Pulmonary volumes, respiratory muscle strength, peak cough flow and chest wall kinematics by optoelectronic plethysmography were studied in 8 patients and 12 healthy subjects as controls. Chest wall volume was modeled as the sum of volumes of the rib cage and abdomen. The plot of the volumes of upper to lower rib cage allowed assessment of rib cage distortion. Unlike controls, patients were unable to reduce end-expiratory chest wall volume, and exhibited greater rib cage distortion during cough. Peak cough flow was negatively correlated with rib cage distortion (the greater the former, the smaller the latter), but not with respiratory muscle strength. In conclusion, insufficient deflation of chest wall compartments and marked rib cage distortion resulted in cough ineffectiveness in these neuromuscular patients.