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.
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.
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.
Our findings suggest that OSM activated the sense of inspiratory flow that achieved dyspnea relief in patients with COPD.
UMIN Clinical Trials Registry (UMIN-CTR); No.: UMIN000033822; URL: https://www.umin.ac.jp/ctr/index.htm
l-Menthol - a new treatment for breathlessness? Kanezaki, Masashi; Terada, Kunihiko; Ebihara, Satoru
Current opinion in supportive & palliative care,
12/2021, Volume:
15, Issue:
4
Journal Article
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.
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.
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.
There is considerable heterogeneity among patients with emphysematous chronic obstructive pulmonary disease (COPD). We hypothesised that in addition to emphysema severity, ventilation distribution in ...emphysematous regions would be associated with clinical-physiological impairments in these patients.
To evaluate whether the discordance between respiratory volume change distributions (from expiration to inspiration) in emphysematous and non-emphysematous regions affects COPD outcomes using two cohorts.
Emphysema was quantified using a low attenuation volume percentage on inspiratory CT (iLAV%). Local respiratory volume changes were calculated using non-rigidly registered expiratory/inspiratory CT. The Ventilation Discordance Index (VDI) represented the log-transformed Wasserstein distance quantifying discordance between respiratory volume change distributions in emphysematous and non-emphysematous regions.
Patients with COPD in the first cohort (n=221) were classified into minimal emphysema (iLAV% <10%; n=113) and established emphysema with high VDI and low VDI groups (n=46 and 62, respectively). Forced expiratory volume in 1 s (FEV
) was lower in the low VDI group than in the other groups, with no difference between the high VDI and minimal emphysema groups. Higher iLAV%, more severe airway disease and hyperventilated emphysematous regions in the upper-middle lobes were independently associated with lower VDI. The second cohort analyses (n=93) confirmed these findings and showed greater annual FEV
decline and higher mortality in the low VDI group than in the high VDI group independent of iLAV% and airway disease on CT.
Lower VDI is associated with severe airflow limitation and higher mortality independent of emphysema severity and airway morphological changes in patients with emphysematous COPD.
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.
Interstitial lung abnormalities (ILAs) on CT may affect the clinical outcomes in patients with chronic obstructive pulmonary disease (COPD), but their quantification remains unestablished. This study ...examined whether artificial intelligence (AI)-based segmentation could be applied to identify ILAs using two COPD cohorts.
ILAs were diagnosed visually based on the Fleischner Society definition. Using an AI-based method, ground-glass opacities, reticulations, and honeycombing were segmented, and their volumes were summed to obtain the percentage ratio of interstitial lung disease-associated volume to total lung volume (ILDvol%). The optimal ILDvol% threshold for ILA detection was determined in cross-sectional data of the discovery and validation cohorts. The 5-year longitudinal changes in ILDvol% were calculated in discovery cohort patients who underwent baseline and follow-up CT scans.
ILAs were found in 32 (14%) and 15 (10%) patients with COPD in the discovery (n = 234) and validation (n = 153) cohorts, respectively. ILDvol% was higher in patients with ILAs than in those without ILA in both cohorts. The optimal ILDvol% threshold in the discovery cohort was 1.203%, and good sensitivity and specificity (93.3% and 76.3%) were confirmed in the validation cohort. 124 patients took follow-up CT scan during 5 ± 1 years. 8 out of 124 patients (7%) developed ILAs. In a multivariable model, an increase in ILDvol% was associated with ILA development after adjusting for age, sex, BMI, and smoking exposure.
AI-based CT quantification of ILDvol% may be a reproducible method for identifying and monitoring ILAs in patients with COPD.
Background: It is unclear whether an abnormal swallowing reflex affects COPD exacerbations. This study investigated the prevalence of
abnormal swallowing reflexes and its relationship with COPD ...exacerbation prospectively. We also clarified its association
with gastroesophageal reflux disease (GERD) and airway bacterial colonization.
Methods: Swallowing reflex and serum C-reactive protein (CRP) levels were examined in subjects with stable COPD and in control subjects.
Concurrently, GERD symptoms were assessed using a self-reported questionnaire, and sputum bacterial cultures were investigated
in the same subjects. Exacerbations were counted prospectively during the following 12 months.
Results: The study group comprised 67 subjects with COPD and 19 controls. The prevalence of abnormal swallowing reflex was significantly
higher in subjects with COPD (22/67) than controls (1/19; P = .02). Among subjects with COPD, the serum CRP level, GERD symptoms, isolation of sputum bacteria, and the frequency of
exacerbations were significantly increased in those with abnormal swallowing reflexes compared with controls (2.72 vs 1.04
mg/L, P = .04, for serum CRP level; 6.75 vs 4.10 points, P = .04, for GERD symptoms; 5/11 vs 3/22, P = .04, for the isolation of sputum bacteria; and 2.82 vs 1.56/y, P = .007, for the annual frequency of exacerbations). Multivariable analysis confirmed that abnormal swallowing reflex was
significantly associated with frequent exacerbations (⥠3/y; P = 0.01).
Conclusions: Abnormal swallowing reflexes frequently occurred in subjects with COPD and predisposed them to exacerbations. Abnormal swallowing
reflexes in COPD might be affected by the comorbidity of GERD, and cause bacterial colonization.
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.
Osteoporosis is one of the important systemic features of COPD. Although COPD itself is regarded as one risk factor for osteoporosis, the relationship between the extent of emphysema and reduced bone ...density is still unclear. Our first aim was therefore to measure vertebral bone density and the percentage of low-attenuation area (LAA%) in the lungs using chest CT scans in COPD patients. Our second aim was to investigate the relationships among CT scan measurements, anthropometric parameters, and pulmonary function.
Chest CT scans and pulmonary function tests were performed in 65 male patients with COPD. Using CT images, the CT scan density of the thoracic and lumbar vertebrae (T4, T7, T10, and L1) and the LAA% were measured quantitatively, and their correlations were analyzed.
Linear regression analyses revealed that LAA% had a significant negative correlation with bone mineral density (BMD) r = −0.522. In addition, multiple regression analysis showed that only LAA% and body mass index (BMI) were predictive of BMD among age, BMI, smoking index, FEV1, arterial blood gas, and LAA%.
The extent of pulmonary emphysema significantly correlated with reduced bone density. Our study suggested that COPD itself could be a risk factor for osteoporosis and that chest CT scanning is useful for the management of COPD as a systemic disease.
Pulmonary abscesses and pyothorax are bacterial infections believed to be caused primarily by oral microbes. However, past reports addressing such infections have not provided genetic evidence and ...lack accuracy, as they used samples that had passed through the oral cavity. The aim of this study was to determine whether genetically identical bacterial strains exist in both the oral microbiota and pus specimens that were obtained percutaneously from pulmonary abscesses and pyothorax, without oral contamination. First, bacteria isolated from pus were identified by 16S rRNA gene sequencing. It was then determined by quantitative PCR using bacterial-species-specific primers that DNA extracted from paired patient oral swab sample suspensions contained the same species. This demonstrated sufficient levels of bacterial DNA of the targeted species to use for further analysis in 8 of 31 strains. Therefore, the whole-genome sequences of these eight strains were subsequently determined and compared against an open database of the same species. Five strain-specific primers were synthesized for each of the eight strains. DNA extracted from the paired oral swab sample suspensions of the corresponding patients was PCR amplified using five strain-specific primers. The results provided strong evidence that certain pus-derived bacterial strains were of oral origin. Furthermore, this two-step identification process provides a novel method that will contribute to the study of certain pathogens of the microbiota.
We present direct genetic evidence that some of the bacteria in pulmonary abscesses and pyothorax are derived from the oral flora. This is the first report describing the presence of genetically homologous strains both in pus from pulmonary abscesses and pyothorax and in swab samples from the mouth. We developed a new method incorporating quantitative PCR and next-generation sequencing and successfully prevented contamination of pus specimens with oral bacteria by percutaneous sample collection. The new genetic method would be useful for enabling investigations on other miscellaneous flora; for example, detection of pathogens from the intestinal flora at the strain level.
Dyspnoea is a risk factor for mortality in patients with chronic obstructive pulmonary disease (COPD) 1. Awareness of the magnitude of respiratory drive to the respiratory muscles contributes to ...dyspnoea 2. In line with this mechanism, elevated respiratory neural drive during hospitalisation and at hospital discharge, predicts readmission and mortality in patients with acute exacerbation of COPD 3, 4. Furthermore, patients with COPD who experienced frequent exacerbations had heightened dyspnoea due to hypercapnia, compared with those with infrequent exacerbations 5. Therefore, changes in the afferent and efferent loops involved in dyspnoea contribute to COPD exacerbations.
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
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