Pulmonary rehabilitation (PR) is able to improve dyspnea, endurance capacity, and health-related quality of life in chronic obstructive pulmonary disease (COPD) patients, but it is rarely used in ...China. This study aimed to assess the effectiveness and safety of PR after exacerbation of COPD.
Patients admitted to hospital due to an exacerbation of COPD were randomized to receive either PR or routine care (control group). The PR program was performed from the second day of admission until discharge. The pre-post changes in 6-minute walk distance (6MWD), self-reported quality of life (QOL) assessed by CAT score and CRQ-SAS score, and activity of daily life assessed by ADL-D score were determined. The perceived end-effort dyspnea (Borg scale) was measured throughout the study.
A total of 101 patients were enrolled, of whom 7 withdrew after randomization, and 94 completed this study. There were 66 patients in the PR group and 28 in the control group. The 6MWD, resting SpO2, and exercise Borg dyspnea score were significantly improved in the PR group. In addition, the PR group had greater improvement in the total CRQ-SAS score and had a lower CAT score. Significant improvements were also found in the ADL-D and BODE index in the PR group. No adverse events were recorded during exercise.
Our study provides evidence that it is safe and feasible to apply an early PR in patients with acute exacerbation of COPD.
Increasing evidence indicates that gut microbiota plays an important role in cancer progression. However, the underlying mechanism remains largely unknown. Here, we report that broad-spectrum ...antibiotics (ABX) treatment leads to enhanced metastasis by the alteration of gut microbiome composition.
Cancer LLC and B16-F10 cell metastasis mouse models, and microarray/RNA sequencing analysis were used to reveal the regulatory functions of microbiota-mediated circular RNA (circRNA)/microRNA (miRNA) networks that may contribute to cancer metastasis.
The specific pathogen-free (SPF) mice with ABX treatment demonstrated enhanced lung metastasis. Fecal microbiota transplantation (FMT) from SPF mice or Bifidobacterium into germ-free mice significantly suppressed lung metastasis. Mechanistically, gut microbiota impacts circRNA expression to regulate levels of corresponding miRNAs. Specifically, such modulations of gut microbiota inhibit mmu_circ_0000730 expression in an IL-11-dependent manner. Bioinformatics analysis combined with luciferase reporter assays revealed reciprocal repression between mmu_circ_0000730 and mmu-miR-466i-3p. We further showed that both mmu-miR-466i-3p and mmu-miR-466 f-3p suppresses a number of genes involved in epithelial-mesenchymal transition (EMT) and stemness of cancer stem cells such as SOX9.
These results provide evidence of a previously unrecognized regulatory role of non-coding RNAs in microbiota-mediated cancer metastasis, and thus, the microbiome may serve as a therapeutic target.
Objective
This study was performed to establish a novel model of citric acid-induced chronic cough in guinea pigs and to investigate the pathogenesis of cough hypersensitivity.
Methods
Healthy ...conscious guinea pigs inhaled citric acid (0.4 M) for 3 minutes twice daily for 25 days. Cough reactivity was evaluated, substance P (SP) and calcitonin gene-related peptide (CGRP) in bronchoalveolar lavage fluid were detected, and transient receptor potential cation channel subfamily V member 1 (TRPV1) protein expression in the trachea and bronchus was determined. Tracheal and bronchial tissues were examined for TRPV1.
Results
Inhalation of 0.4 M citric acid increased coughing in a time-dependent manner: coughing peaked at 15 days and reached the lowest level at 25 days. This was accompanied by similar changes in SP, CGRP, and TRPV1 protein expression. TRPV1 was mainly observed in the mucosal and submucosal layer of the trachea and bronchi. The areas of TRPV1 positivity in the trachea and bronchi of citric acid-treated animals were significantly larger than in the control group.
Conclusions
Repeated inhalation of citric acid can be employed to establish a chronic cough model in guinea pigs. Cough hypersensitivity in this model is related to tracheal TRPV1 activation and neurogenic inflammation.
Background:
The management of refractory chronic cough (RCC) is a great challenge. Neuromodulators have long been used for RCC with imperfect efficacy.
Objectives:
We summarized the outcomes of the ...current treatments used at our specialist cough clinic, which provides a guideline-led service and real-world experience for the future management of RCC.
Design:
This is a single-centre retrospective observational cohort study.
Methods:
Consecutive RCC patients (the first clinic visit between January 2016 and May 2021) were included into this observational cohort study. Medical records in the Chronic Cough Clinical Research Database were fully reviewed using uniform criteria. The included subjects were followed-up for at least 6 months after the final clinic visit via instant messages with the link to self-scaled cough-associated questionnaires.
Results:
Overall, 369 RCC patients were analysed with a median age of 46.6 years and a cough duration of 24.0 months. A total of 10 different treatments were offered. However, 96.2% of patients had been prescribed at least one neuromodulator. One-third of patients had alternative treatments prescribed given the poor response to the initial therapy and 71.3% favourably responded to at least one of the treatments. Gabapentin, deanxit, and baclofen had comparable therapeutic efficacy (56.0%, 56.0%, and 62.5% respectively; p = 0.88) and overall incidences of adverse effects (28.3%, 22.0%, and 32.3% respectively; p = 0.76). However, 19.1 (7.7–41.8) months after the last clinic visit, 65.0% reported improvement (24.9%) or control of their cough (40.1%); 3.8% reported a spontaneous remission and 31.2% still had a severe cough. Both HARQ (n = 97; p < 0.001) and LCQ (n = 58; p < 0.001) demonstrated marked improvement.
Conclusion:
Trying different neuromodulators is a pragmatic strategy for RCC, which helped around two-thirds of patients. Relapse is common on withdrawal or reduction of dosage. Novel medication for RCC is an urgent clinical need.
Plain language summary
This is the first report that fully represented a guideline-led treatment protocol for refractory chronic cough (RCC) based on a large series of patients, which evaluated the short- and long-term effects of the currently available treatments for RCC. We found that the therapeutic trial of different neuromodulators is a pragmatic strategy, which helped around two-thirds of patients. Gabapentin, deanxit (flupentixol/melitracen), and baclofen had similar therapeutic outcomes. This study may offer real-world experience for the future management of RCC.
Fractional exhaled nitric oxide (FeNO) measured at multiple exhalation flow rates can be used as a biomarker to differentiate central and peripheral airway inflammation. However, the role of alveolar ...nitric oxide (CaNO) indicating peripheral airway inflammation remains unclear in gastroesophageal reflux-associated cough (GERC).
We aimed to characterize the changes in alveolar nitric oxide (CaNO) and determine its clinical implication in GERC.
This is a single-center prospective observational study.
FeNOs at exhalation flow rates of 50 and 200 ml/s were measured in 102 patients with GERC and 134 patients with other causes of chronic cough (non-GERC). CaNO was calculated based on a two-compartment model and the factors associated with CaNO were analyzed. The effect of anti-reflux therapy on CaNO was examined in 26 GERC patients with elevated CaNO.
CaNO was significantly elevated in GERC compared with that in non-GERC (4.6 ± 4.4 ppb
2.8 ± 2.3 ppb,
< 0.001). GERC patients with high CaNO (>5 ppb) had more proximal reflux events (24 ± 15
9 ± 9 episodes,
= 0.001) and a higher level of pepsin (984.8 ± 492.5
634.5 ± 626.4 pg/ml,
= 0.002) in sputum supernatant than those with normal CaNO. More GERC patients with high CaNO required intensified anti-reflux therapy (χ
= 3.963,
= 0.046), as predicted by a sensitivity of 41.7% and specificity of 83.3%. Cough relief paralleled a significant improvement in CaNO (8.3 ± 3.0
4.8 ± 2.6 ppb,
< 0.001).
Peripheral airway inflammation can be assessed by CaNO measurement in GERC. High CaNO indicates potential micro-aspiration and may predict a necessity for intensified anti-reflux therapy.
Background:
Gabapentin is recommended for the treatment of chronic refractory cough (CRC). This study aims to identify its therapeutic predictors in a prospective clinical study.
Methods:
A total of ...179 patients with CRC were treated with gabapentin. Prior to the therapy, all patients were assessed by Hull Airway Reflux Questionnaire (HARQ) and inhaled capsaicin challenge. When the treatment ended and cough resolution was confirmed, a stepwise logistic regression analysis was performed to identify the therapeutic predictors for gabapentin and to establish the prediction equation.
Results:
Gabapentin treatment achieved a therapeutic success rate of 66.48%. HARQ scores were significantly higher in responders than non-responders to gabapentin (29.79 ± 9.58 versus 21.95 ± 7.83, t = –3.685, p <0.001), which were positively related to the therapeutic efficacy of gabapentin (r = 0.433, p <0.001). The optimal cutoff point of 21.50 in HARQ presented with a moderate ability to predict gabapentin efficacy, with a sensitivity of 84.60% and specificity of 63.60%. Multiple logistic regression identified items of “A tickle in your throat, or a lump in your throat” (OR = 7.927, p = 0.005), “Cough when you get out of bed in the morning” (OR = 7.016, p = 0.045), and “Cough with eating” (OR = 6.689, p = 0.011) as independent predictors. The established logistic regression equation predicted 83.72% of the treatment success rate of gabapentin, which was verified by consequent preliminary revalidating study in 59 patients.
Conclusion:
HARQ may be useful to screen patients with CRC most likely responsive to gabapentin, and help improve the therapeutic success.
Trial registration:
http://www.chictr.org/; No.: ChiCTR-ONC-13003123
Objectives:
To elucidate the accuracy and advantages of Multichannel intraluminal impedance-pH monitoring (MII-pH) in diagnosing gastroesophageal reflux-induced chronic cough (GERC).
Methods:
The ...patients with suspected GERC were recruited and underwent MII-pH, GERC was confirmed by subsequent anti-reflux treatment despite the findings of MII-pH. Its diagnostic accuracy in identifying GERC were evaluated by receiver operating characteristic (ROC) analysis and compared with that of 24-h esophageal pH monitoring.
Results:
Among 158 patients completing both MII-pH and anti-reflux therapy, GERC was diagnosed in 136 patients, including acid GERC in 96 patients (70.6%), non-acid GERC in 30 patients (22.0%), neither one of both GERC in 10 patients (7.4%). For the identification of GERC, MII-pH presented with the sensitivity of 92.6%, specificity of 63.6%, positive predictive value of 94.0%, negative predictive value of 58.3% and area under ROC curve of 0.863, which was totally superior to 24-h esophageal pH monitoring. As the essential criteria of MII-pH, esophageal acid exposure time and symptom associated probability had a limited diagnostic value when used alone, but improved greatly the diagnostic yield when used in combination, even with a suboptimal efficacy.
Conclusion:
MII-pH is a more sensitive test for identifying GERC, but with a suboptimal diagnostic efficacy.
Patients not eligible for any biologic treatments were characterized by the highest FeNO (33.2 ppb, P < 0.001), with raised sputum eosinophils and BEC (270/μL) and none received OCS therapy. Because ...the UK National Health and Care Institute has advocated the use of these biologics using different criteria (https://www.nice.org.uk/guidance/TA751/chapter/1-Recommendations), we have examined these conditions such as the need for having more than four severe exacerbations in the previous year and the combination of BEC ≥150/μL plus FeNO ≥25 ppb for consideration of severe asthma patients for anti-IL4Rα. ...extending the cut-off point of 1, 2, 3, or 4 exacerbations in the previous year, those eligible for the biologic therapies would be 58.8%, 38.5%, 23.0%, and 15.3%, respectively Supplementary Table 1, http://links.lww.com/CM9/B402. ...many of the 42.0% of severe asthma patients not eligible for biologic therapies represent those who do not report two or more exacerbations in the previous year, particularly in those with atopy and high BECs. ...this study reveals that T2-high asthma is the predominant phenotype in patients with severe asthma in the C-BIOPRED cohort and remains relatively stable after a 1-year longitudinal visit.
Background Empirical therapy has been recommended as an initial clinical approach for treating gastroesophageal reflux-induced chronic cough (GERC). This study compared the predictive accuracy of the ...Gastroesophageal Reflux Disease Questionnaire (GerdQ) with the accuracy of multichannel intraluminal impedance pH monitoring (MII-pH) for GERC. Methods A total of 126 consecutive patients with potential GERC were recruited to undergo MII-pH and complete the GerdQ. A final diagnosis of GERC was made after favorable response to consequent medicinal antireflux therapy, regardless of laboratory findings. The predictive accuracy of the GerdQ for GERC was assessed and compared with that of MII-pH. Results GERC was confirmed in 102 of 126 patients (81.0%); cough was due to acid reflux in 55 (53.9%) and nonacid reflux in 47 (46.1%). The optimal cutoff point of the GerdQ for predicting GERC was defined as 8.0 according to the highest Youden index of 0.584, with a sensitivity of 66.7%, specificity of 91.7%, positive predictive value of 97.1%, and negative predictive value of 42.9%. A subanalysis for only acid GERC showed further improvement in the predictive accuracy of the GerdQ, corresponding to a sensitivity of 90.9%, specificity of 78.6%, positive predictive value of 71.4%, and negative predictive value of 96.4%. However, a meaningful GerdQ cutoff point for prediction of nonacid GERC could not be determined. In general, MII-pH was superior to the GerdQ for predicting GERC and acid GERC. Conclusions The GerdQ can be used for predicting acid GERC but not nonacid GERC and is inferior to MII-pH. Trial registry Chinese Clinical Trial Registry; No.: ChiCTR-ODT-12001899; URL: www.chictr.org
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