Chronic obstructive pulmonary disease features in patients visiting primary respiratory clinic and tertiary hospital in Japan.

Pulmonologists in primary care clinics are positioned between those in tertiary hospitals and general practitioners in clinics and are anticipated to promote hospital-clinic collaboration for patients with chronic obstructive pulmonary disease (COPD). However, the clinical features of patients in primary respiratory clinics are unclear. This multicenter study cross-sectionally compared the characteristics of patients with COPD in a respiratory clinic (n = 69) with those in a university hospital (n = 124). More patients visited the clinic for symptom relief without a referral, whereas more visited the hospital for consultation of abnormal spirometry/computed tomography (CT). The patients in the clinic showed female predilection, higher prevalence of current smokers, severe dyspnea, and concomitant heart failure, and higher CT-measured cross-sectional area ratio of pectoralis muscle to adjacent subcutaneous adipose tissue compared to those in the hospital (all p < 0.05). The observed differences between the two groups suggest the need to establish the role of primary pulmonologists in hospital-clinic collaboration for better COPD management.

Limitations of a 6-min walk test to assess the efficacy of menthol for breathlessness.

l-Menthol is a novel treatment option for breathlessness in patients with COPD. However, the clinical application of menthol for the treatment of exertional breathlessness in these patients warrants further research. https://bit.ly/3D6rLiJ.

Associations of pulmonary and extrapulmonary computed tomographic manifestations with impaired physical activity in symptomatic patients with chronic obstructive pulmonary disease.

In patients with chronic obstructive pulmonary disease (COPD), emphysema, airway disease, and extrapulmonary comorbidities may cause various symptoms and impair physical activity. To investigate the relative associations of pulmonary and extrapulmonary manifestations with physical activity in symptomatic patients, this study enrolled 193 patients with COPD who underwent chest inspiratory/expiratory CT and completed COPD assessment test (CAT) and the Life-Space Assessment (LSA) questionnaires to evaluate symptom and physical activity. In symptomatic patients (CAT ≥ 10, n = 100), emphysema on inspiratory CT and air-trapping on expiratory CT were more severe and height-adjusted cross-sectional areas of pectoralis muscles (PM index) and adjacent subcutaneous adipose tissue (SAT index) on inspiratory CT were smaller in those with impaired physical activity (LSA < 60) than those without. In contrast, these findings were not observed in less symptomatic patients (CAT < 10). In multivariable analyses of the symptomatic patients, severe air-trapping and lower PM index and SAT index, but not CT-measured thoracic vertebrae bone density and coronary artery calcification, were associated with impaired physical activity. These suggest that increased air-trapping and decreased skeletal muscle and subcutaneous adipose tissue quantity are independently associated with impaired physical activity in symptomatic patients with COPD.

Linguistic Validation of the Japanese Version of the Multidimensional Dyspnea Profile and Relation to Physical Activity in Patients with COPD.

PURPOSE: This study aimed to develop a linguistically validated Japanese translation of the multidimensional dyspnea profile (MDP) and assess whether worsening of dyspnea's sensory and affective domains during exercise had detrimental effects on physical activity in stable outpatients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: The Japanese version of the MDP was prepared in collaboration with Mapi Research Trust (Lyon, France) after the approval of the developer. Physical activity was assessed using a 3-axis accelerometer. Dyspnea upon exertion was investigated using a 3-minute step test. RESULTS: The Japanese version of the MDP was obtained and validated linguistically. Air-hunger was significantly associated with total calories from walking (r = - 0.47, p < 0.05), while anxiety and depression were significantly correlated with both the amount and intensity of physical activity (r = - 0.49, p < 0.05, and r = - 0.46, p < 0.05, respectively). CONCLUSION: The Japanese version of the MDP was suggested to reflect both pulmonary functions, ventilatory response during exercise, and intensity and amount of physical activity in patients with COPD.

l-Menthol - a new treatment for breathlessness?

PURPOSE OF REVIEW: In patients with advanced chronic obstructive pulmonary disease (COPD), it is challenging to treat breathlessness. In addition, novel palliative interventions are required for multiple perspectives of breathlessness that may still be present after disease-specific therapies. This review provides an overview of the mechanisms and effects of l-menthol on breathlessness by covering the latest relevant papers. RECENT FINDINGS: A literature review identified one randomized controlled trial assessing the effect of l-menthol on relieving breathlessness in patients with COPD. It has been reported that the mechanism of relieving breathlessness partly involves stimulation of the trigeminal nerve by the cooling sensation of l-menthol, which gives a cognitive illusion of inspiratory flow perception. The effect of l-menthol on breathlessness caused by exertion has been reported in healthy subjects but not yet in patients with breathlessness. SUMMARY: The effect of l-menthol on the sensory-emotional dimensions of laboratory-induced breathlessness in patients with COPD has been described in a clinical trial. Further studies are warranted to investigate its application to inspiratory muscle training and its effects in combination with exercise training.

Exertional multidimensional dyspnoea predicts exacerbation in stable outpatients with COPD.

This study assessed the sensory and emotional aspects of breathlessness under the same exercise load in patients with COPD. Breathing discomfort with constant exercise predicted exacerbations within 1 year. https://bit.ly/3l2oA4A.

Effects of Sarcopenia on Ventilatory Behavior and the Multidimensional Nature of Dyspnea in Patients With Chronic Obstructive Pulmonary Disease.

OBJECTIVES: This study tested the hypothesis that sarcopenia, a common extrapulmonary feature of chronic obstructive pulmonary disease (COPD), can affect ventilatory behavior, and worsen the multidimensional nature of dyspnea in patients with COPD. DESIGN: Cross-sectional survey study. SETTING: and Participants: Stable outpatients with COPD encountered in general practice and respiratory clinic. METHOD: Sarcopenia was diagnosed according to an appendicular skeletal muscle mass index based on measurements of electrical impedance and handgrip strength. Exertional dyspnea was tested using a 3-minute Step Test and a 6-minute Walk Test. The dimensions of dyspnea were assessed by a multidimensional dyspnea profile. RESULTS: Of 60 stable patients with COPD, 16 met the criteria for sarcopenia. During the 3-minute Step Test, minute ventilation as a proportion of exercise time, tidal volume as a proportion of inspiratory capacity, the change in inspiratory capacity, and ventilation as a proportion of maximal voluntary ventilation did not differ between patients with and without sarcopenia. Patients with sarcopenia exhibited lower evolution of tidal volume, higher evolution of respiratory frequency versus ventilation and breathing discomfort on the 3-minute Step Test, as well as increased physical breathing effort on the 6-minute Walk Test, compared with those without sarcopenia. In a multivariable model adjusted using inverse probability weighting, sarcopenia was independently associated with breathing discomfort during the 3-minute Step Test and physical breathing effort during the 6-minute Walk Test. CONCLUSIONS AND IMPLICATIONS: Sarcopenia may be associated with shallow breathing and diverse sensory and affective components of exertional dyspnea in patients with COPD. The study indicates that improvement of the rapid breathing pattern may offer unique ways to alleviate dyspnea in older patients with COPD and sarcopenia.

Effect of Olfactory Stimulation by L-Menthol on Laboratory-Induced Dyspnea in COPD.

BACKGROUND: Inhalation of L-menthol as a transient receptor potential melastatin 8 agonist induces a cooling sensation in the airway. This cooling sensation induced through olfactory stimulation by L-menthol (OSM) alleviates dyspnea in healthy humans. Therefore, we investigated effects of OSM on the neural respiratory drive (NRD) and multidimensional aspects of dyspnea induced by inspiratory resistive loaded breathing in COPD. METHODS: In total, 28 patients with COPD and 14 control participants were included in this randomized, single-blinded, placebo-controlled, crossover study. OSM was administered using an L-menthol-scented patch, whereas placebo was administered using olfactory stimulation by strawberry-scented patch: placebo (OSP). Sham condition was measured by breathing through a face mask without a OSP. Dyspnea was evoked by breathing through the inspiratory resistance of 20 or 30 cm H2O/L/s and measured using the Multidimensional Dyspnea Profile. NRD was estimated using the electromyogram activities of the parasternal intercostal muscles. RESULTS: Compared with sham and OSP, OSM did not alter the breathing pattern/timing and NRD during inspiratory resistive loading; however, it significantly alleviated the physical and mental breathing effort, air hunger, breathing discomfort, anxiety, and fear during inspiratory resistive loaded breathing in patients with COPD. However, although OSM reduced the air hunger, mental breathing effort, and unpleasantness, no significant improvement on affective dimension of dyspnea by OSM was observed in control participants. CONCLUSIONS: Our findings suggest that OSM activated the sense of inspiratory flow that achieved dyspnea relief in patients with COPD. TRIAL REGISTRY: UMIN Clinical Trials Registry (UMIN-CTR); No.: UMIN000033822; URL: https://www.umin.ac.jp/ctr/index.htm.

Effect of facial skin cooling induced by a handheld fan on the cough reflex threshold and urge to cough induced by citric acid.

Facial skin cooling induced by a handheld fan alleviates the cough reflex and the urge to cough induced by citric acid http://bit.ly/2m1kzAP.

Alleviation of Dyspnea Sensation by Phototherapy in Healthy Adults.

BACKGROUND: Because both dyspnea and pain have common features from a clinical and physiologic point of view, we hypothesized that stellate ganglion irradiation by using a linear polarized near-infrared ray device, which is often used for pain management, might be applicable for dyspnea relief. To evaluate the use of stellate ganglion irradiation as a novel noninvasive treatment for dyspnea, we investigated the influence of stellate ganglion irradiation on dyspnea. METHODS: Perceptions of dyspnea were examined with or without stellate ganglion irradiation in 28 healthy adults. The sensation of breathing difficulty was induced by a two-way non-rebreathing valves with linear inspiratory resistance (R) of 0, 10, 20, and 30 cm H2O/L/s. Dyspnea was evaluated with the modified Borg scale to determine subjects' discomfort level. Stellate ganglion irradiation was performed by intermittent irradiation near the bilateral stellate ganglion by using a linear polarized near-infrared ray device. RESULTS: There were significant changes from baseline at R = 10 cm H2O/L/s (P = .007), R = 20 cm H2O/L/s (P = .005), and R = 30 cm H2O/L/s (P = .009). For each resistive load, the mean dyspnea sensation score was lower with stellate ganglion irradiation compared with sham irradiation, with significant differences (P = .003 at R = 0 cm H2O/L/s; P < .001 at R = 10, 20, 30 cm H2O/L/s). There was a significantly lower slope of the dyspnea response for the linear regression of the loads and Borg scores in the stellate ganglion irradiation versus sham treatment (P = .003). CONCLUSIONS: Stellate ganglion irradiation significantly alleviated dyspnea induced by an external inspiratory load in healthy adults. Stellate ganglion irradiation might be an option to treat dyspnea in some cases. Further studies in individuals with diverse types of dyspnea and clinical settings are warranted.

Tongue Protrusion Strength in Arousal State Is Predictive of the Airway Patency in Obstructive Sleep Apnea.

Contraction of the genioglossus affects either tongue protrusion strength or dilating forces of the upper airway. The upper airway in patients with obstructive sleep apnea (OSA) is thought to collapse during sleep, at least in part because of a sleep related reduction in genioglossus muscle activity. Thus, although tongue protrusion strength by genioglossus activity during sleep contributes to the maintenance of airway patency in patients with OSA, the relationship between tongue protrusion strength in the arousal state and obstructive sleep apnea has not been fully elucidated. Conventional method of tongue protrusion strength cannot be used to evaluate in edentulous subjects and/or subjects with the decreased biting force. In this study, employing a novel measurement method that does not require biting a transducer, we investigated relationships between the tongue protrusion strength and polysomnographic findings. We enrolled twenty normal subjects and 26 subjects with OSA. All subjects completed the measurement of tongue protrusion strength. Each subject with OSA was evaluated by full polysomnography. The degree of tongue protrusion strength was assessed by maximum voluntary contraction against the tongue depressor connected with a strain gauge dynamometer. The tongue protrusion strength was negatively correlated with obstructive apnea time, apnea index (AI) and the percent of sleep stage 2 (r = -0.61, p < 0.0001, r = -0.41 p = 0.03 and r = -0.39 p = 0.04, respectively). Tongue protrusion strength measured in the arousal state is predictive of the airway patency during sleep in OSA.

Distractive Auditory Stimuli Alleviate the Perception of Dyspnea Induced by Low-Intensity Exercise in Elderly Subjects With COPD.

BACKGROUND: Although recent studies have shown that distractive auditory stimuli (DAS) in the form of music increase adherence to exercise in subjects with COPD, the effect of DAS on dyspnea induced by low-intensity, constant-load exercise in elderly patients with COPD has not been elucidated. Therefore, the purpose of this study was to investigate the effect of DAS on the perception of dyspnea induced by low-intensity, constant-load exercise in elderly subjects with COPD. METHODS: We enrolled 16 male out-patients with COPD. Subjects completed cycling exercises with and without DAS at 40% maximum oxygen consumption. They were asked to rate their perception of dyspnea using the modified Borg scale every 3 min during exercise and every 1 min during the recovery period. RESULTS: Dyspnea perception during low-intensity exercise showed a significant correlation between the exercise condition (DAS and control) and exercise duration (P = .04). Exercise-induced dyspnea perception under the DAS condition was significantly lower than that under the control condition from 18 min after the start of exercise to 3 min after the end of exercise (18, 20, 21, 22, and 23 min, P = .01, P < .001, P = .009, P = .006, and P = .006, respectively). However, oxygen consumption and ventilation in response to low-intensity exercise did not significantly differ in the DAS and control conditions (P = .39 and .14, respectively) CONCLUSIONS: Our results suggest that DAS is a non-pharmacologic therapy that can be used to reduce the dyspneic sensation in elderly patients with COPD.

Effect of Dyspnea Induced by Breath-holding on Maximal Muscular Strength of Patients with COPD.

[Purpose] The purpose of the present study was to clarify the effect of dyspnea induced by breath-holding on maximum muscular strength of patients with COPD. [Subjects] This study recruited 14 COPD subjects via public posting. [Methods] Dyspnea was assessed by the modified Borg scale. The subject asked to stop breathing at end-expiration and to hold their breath with a nose clip for as long as possible. Both total breath-holding time and threshold time of dyspnea were measured with a chronograph. Dyspnea reserve time (DRT) was defined by subtracting the threshold time of perception dyspnea from total breath-holding time in order to calculate the 50% DRT. The muscular strengths of maximal handgrip contraction were measured at baseline, 50% threshold time of dyspnea (subliminal point of dyspnea), and the 50% DRT (supraliminal point of dyspnea). [Results] The maximal handgrip at the supraliminal point of dyspnea was significantly lower than the baseline and subliminal point of dyspnea values. There was no statistically significant difference in maximal muscular strength between baseline and the subliminal point of dyspnea value. [Conclusion] The present results demonstrate that dyspnea induced by breath-holding aggravates weakness in the maximum muscular strength of patients with COPD.

Urge-to-cough and dyspnea conceal perception of pain in healthy adults.

Although dyspnea has been shown to attenuate pain, whether urge-to-cough, a respiratory sensation preceding cough, exerts a similar inhibitory effect on pain has not been clarified. We examined the effects of both urge-to-cough and dyspnea on pain induced by thermal noxious stimuli. Urge-to-cough was induced by citric acid challenge and dyspnea was induced by external inspiratory resistive loads. During inductions of two respiratory sensations, perception of pain was assessed by thermal pain threshold (TPTh) and tolerance (TPTo). TPTh and TPTo were significantly increased accompanied by increases in perception of both urge-to-cough and dyspnea. Fractional change in TPTh during dyspnea was significantly correlated with that during urge-to-cough. Fractional change in TPTo during dyspnea was significantly correlated with that during urge-to-cough. The study suggests that both two distinct respiratory sensations, i.e., urge-to-cough and dyspnea may harbor perception of pain. Further studies investigating interactions among these sensations in clinical settings are warranted.

Effect of cigarette smoking on cough reflex induced by TRPV1 and TRPA1 stimulations.

BACKGROUND: Recent studies have shown that neurogenic inflammation induced by cigarette smoke is inhibited by TRPA1 antagonist, but not by TRPV1 antagonist. Since cough reflex sensitivity is known to be modified by smoking status, we investigated the effects of cigarette smoking on TRPA1- and TRPV1-induced cough and urge-to-cough in healthy males. METHODS: Twenty-six healthy never-smokers and 30 healthy current smokers were recruited via public postings. Cough reflex thresholds and urge-to-cough were evaluated by inhalation of capsaicin, a TRPV1 agonist, and cinnamaldehyde, a TRPA1 agonist. The cough reflex thresholds were defined as the lowest concentrations of capsaicin and cinnamaldehyde that elicited two or more coughs (C(2)) and five or more coughs (C(5)), respectively. The urge-to-cough was evaluated using the modified Borg scale. RESULTS: In capsaicin-induced cough, the cough reflex thresholds, as expressed by C(2) and C(5), in current smokers were significantly higher than those in never-smokers (p<0.01 and p<0.001, respectively). The urge-to-cough log-log slopes in current smokers were significantly lower than those of never-smokers (p<0.001). There were no significant differences in the thresholds of the urge-to-cough between never-smokers and current smokers. In cinnamaldehyde-induced cough, there were no significant differences in cough reflex thresholds in C(2) and C(5) between never-smokers and current smokers, nor were there any significant differences in urge-to-cough log-log slope between never-smokers and current smokers. There were no significant differences in the thresholds of the urge-to-cough between never-smokers and current smokers. CONCLUSION: The study suggests that smoking has a differential effect on cough responses between TRPV1 and TRPA1 stimulations.

Aging deteriorated perception of urge-to-cough without changing cough reflex threshold to citric acid in female never-smokers.

BACKGROUND: The effect of aging on the cognitive aspect of cough has not been studied yet. The purpose of this study is to investigate the aging effect on the perception of urge-to-cough in healthy individuals. METHODS: Fourteen young, female, healthy never-smokers were recruited via public postings. Twelve elderly female healthy never-smokers were recruited from a nursing home residence. The cough reflex threshold and the urge-to-cough were evaluated by inhalation of citric acid. The cough reflex sensitivities were defined as the lowest concentration of citric acid that elicited two or more coughs (C2) and five or more coughs (C5). The urge-to-cough was evaluated using a modified the Borg scale. RESULTS: There was no significant difference in the cough reflex threshold to citric acid between young and elderly subjects. The urge-to-cough scores at the concentration of C2 and C5 were significantly smaller in the elderly than young subjects. The urge-to-cough log-log slope in elderly subjects (0.73 ± 0.71 point · L/g) was significantly gentler than those of young subjects (1.35 ± 0.53 point · L/g, p < 0.01). There were no significant differences in the urge-to-cough threshold estimated between young and elderly subjects. CONCLUSIONS: The cough reflex threshold did not differ between young and elderly subjects whereas cognition of urge-to-cough was significantly decreased in elderly subjects in female never-smokers. Objective monitoring of cough might be important in the elderly people.

Gender differences in perceptions of urge to cough and dyspnea induced by citric acid in healthy never smokers.

BACKGROUND: The mechanism of the gender difference in cough reflex threshold has not been clearly elucidated. In the present study, we evaluated gender differences in the cough reflex threshold along with the perceptions of respiratory sensations, urge to cough, and dyspnea. METHODS: Nineteen male and 20 female healthy never smokers were recruited through public postings. The cough reflex threshold and the urge to cough were evaluated by inhalation of citric acid. The perception of dyspnea was evaluated by Borg scores during applications of external inspiratory resistive loads. RESULTS: The cough reflex threshold and suprathreshold to citric acid in women, as expressed by the log transformation of the lowest concentration of citric acid that elicited two or more and five or more coughs, was significantly lower than that in men. The urge-to-cough log-log slope in women (1.47 ± 0.81 point × L/g) was significantly steeper than in men (0.96 ± 0.28 point × L/g; P < .03). There were no significant differences in the urge-to-cough threshold estimated between men and women. The slope of the dyspnea Borg score change during the external inspiratory resistive loads is steeper in women (0.17 ± 0.04 point/cm H2O/L/s) than that in men (0.13 ± 0.05 point/cm H2O/L/s; P < .01). The urge-to-cough slope significantly correlated with the perception of dyspnea slope (r = 0.537; P < .01). CONCLUSIONS: The gender difference in cough reflex threshold accompanied the gender difference in amplification rate of respiratory sensations in the same direction. The higher central gain for common pathways for respiratory sensations may play a role in lower cough reflex threshold in women. Further studies are needed to elucidate this issue.