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1.
Respir Res ; 25(1): 280, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014448

ABSTRACT

BACKGROUND: Morphine relieves dyspnea in various clinical circumstances. Whether or not this applies to patients admitted to intensive care units (ICUs) for acute respiratory failure (ARF) is unknown. We evaluated the efficacy and safety of low-dose morphine on dyspnea in patients admitted to the ICU for ARF. METHODS: In this single-center, double-blind, phase 2, randomized, controlled trial, we assigned non-intubated adults admitted to the ICU for ARF with severe dyspnea, defined by a visual analog scale for dyspnea (dyspnea-VAS) from zero (no dyspnea) to 100 mm (worst imaginable dyspnea) ≥40 mm, to receive a low dose of Morphine Hydrochloride (intravenous titration followed by subcutaneous relay) or Placebo. All patients received standard therapy, including etiological treatment and non-invasive respiratory support. RESULTS: Twenty-two patients were randomized, 11 in each group. The average dyspnea (median [interquartile range]) over 24 hours did not significantly differ between the two groups (40 [25 - 43] mm in the Morphine group vs. 40 [36 - 49] mm in the Placebo group, p=0.411). Dyspnea-VAS was lower in the Morphine group than in the Placebo group at the end of intravenous titration (30 [11 - 30] vs. 35 [30 - 44], p=0.044) and four hours later (18 [10 - 29] vs. 50 [30 - 60], p=0.043). The cumulative probability of intubation was higher in the Morphine group than in the Placebo group (p=0.046) CONCLUSION: In this phase 2 pilot trial, morphine did not improve 24-hour average dyspnea in adult patients with ARF, even though it had a statistically significant immediate effect. Of concern, Morphine use was associated with a higher intubation rate. TRIAL REGISTRATION: The protocol was declared on the ClinicalTrial.gov database (no. NCT04358133) and was published in September 2022.


Subject(s)
Analgesics, Opioid , Dyspnea , Morphine , Humans , Morphine/administration & dosage , Double-Blind Method , Dyspnea/drug therapy , Dyspnea/diagnosis , Male , Female , Middle Aged , Aged , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/adverse effects , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/diagnosis , Treatment Outcome , Adult
4.
J Hosp Palliat Nurs ; 26(4): 195-204, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38901025

ABSTRACT

Dyspnea is the most common and activity-limiting symptom for those with chronic obstructive pulmonary disease (COPD). Treatment is complex, palliative care (PC) dyspnea relief interventions are poorly understood, and PC remains underutilized in COPD despite national guidelines and recommendations. The purpose of this rapid review was to explore the concept of dyspnea and role of PC through the lens of providers, caregivers, and patients with COPD. A systematic approach for synthesis was used to identify 13 articles published between January 2018 and October 2023. Team members compared data via visualization and theme clustering to identify key conclusions describing operationalization of dyspnea, management, and PC implications. Dyspnea operationalization was challenging, with inconsistent measurement and terminology. Dyspnea was a significant burden in COPD and contributed to complexity of treatment. Opioids were used most often to treat dyspnea, but provider perspectives and biases can influence treatment decisions and perceptions of opioid therapy by the patient and caregiver. Evidence-based clinical practice guidelines and policies are needed to clarify the use of opioid therapy for dyspnea management to reduce stigmatization and barriers to treatment. Provider education should emphasize a multipronged approach to treatment of dyspnea in COPD with integration of PC early in the care continuum.


Subject(s)
Dyspnea , Palliative Care , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/therapy , Dyspnea/therapy , Dyspnea/etiology , Dyspnea/drug therapy , Palliative Care/methods , Palliative Care/standards
5.
BMJ Support Palliat Care ; 13(e3): e1126-e1132, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38557730

ABSTRACT

OBJECTIVES: Dyspnoea is a common and distressing symptom in patients with cancer. We aimed to analyse the association between dyspnoea and related factors and to estimate their causal relationship. METHODS: A cross-sectional study was conducted. Patients with cancer with dyspnoea and a mean Numerical Rating Scale (NRS) of ≥3 over 24 hours were enrolled at 10 institutions in Japan from December 2019 to February 2021. The outcomes included dyspnoea, cough and pain NRS over 24 hours, Eastern Cooperative Oncology Group Performance Status, Hospital Anxiety and Depression Scale, Somatosensory Amplification Scale, opioids for dyspnoea and respiratory failure. Path analyses were conducted to estimate the direct and indirect paths with reference to dyspnoea and related factors. RESULTS: A total of 209 patients were enrolled and 208 patients were included in the analysis. Cough worsened dyspnoea (ß=0.136), dyspnoea increased emotional distress (ß=1.104), emotional distress increased somatosensory amplification (ß=0.249) and somatosensory amplification worsened cough (ß=0.053) according to path analysis. CONCLUSION: There may be a vicious circle among dyspnoea and related factors: cough worsened dyspnoea, dyspnoea increased emotional distress, emotional distress increased somatosensory amplification and somatosensory amplification worsened cough. When treating dyspnoea in patients with cancer, managing these factors aimed at interrupting this vicious circle may be useful. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000038820).


Subject(s)
Neoplasms , Humans , Cough/complications , Cross-Sectional Studies , Dyspnea/drug therapy , Neoplasms/complications , Neoplasms/psychology , Psychological Distress
6.
BMC Pulm Med ; 24(1): 156, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38539172

ABSTRACT

BACKGROUND: Chronic cough is a common symptom in patients post the coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the efficacy of inhaled corticosteroids (ICS) and the clinical characteristics of patients with post-COVID-19 chronic cough during the Omicron era. METHODS: An ambispective, longitudinal cohort study was conducted that included patients with post-COVID-19 who attended the respiratory clinic at our hospital between January 1, 2023, and March 31, 2023 with a complaint of persistent cough lasting more than 8 weeks. At 30 and 60 days after the first clinic visit for post-COVID-19 chronic cough, enrolled patients were prospectively followed up. We compared the changes in symptoms and pulmonary function between patients receiving ICS treatment (ICS group) and those not receiving ICS treatment (NICS group) at the two visits. RESULTS: A total of 104 patients with post-COVID-19 chronic cough were enrolled in this study (ICS group, n = 51; NICS group, n = 53). The most common symptoms accompanying post-COVID-19 chronic cough were sputum (58.7%, 61/104) and dyspnea (48.1%, 50/104). Seventy-one (82.6%, 71/86) patients had airway hyperresponsiveness, and 49 patients (47.1%, 49/104) were newly diagnosed with asthma. Most patients (95.2%, 99/104) exhibited improvement at 60 days after the first visit. The pulmonary function parameters of the patients in the ICS group were significantly improved compared to the baseline values (P < 0.05), and the improvement in the FEV1/FVC was significantly greater than that in the NICS group (P = 0.003) after 60 days. CONCLUSIONS: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may contribute to the pathogenesis of asthma, which could be the underlying cause of persistent cough post-COVID-19 infection. Post-COVID-19 chronic cough during the Omicron era was often accompanied by sputum, dyspnea, and airway hyperresponsiveness. ICS treatment did not have a significant impact on symptom management of post-COVID-19 chronic cough; however, it can improve impaired lung function in in these individuals.


Subject(s)
Asthma , COVID-19 , Humans , Chronic Cough , Longitudinal Studies , COVID-19/complications , SARS-CoV-2 , Asthma/complications , Asthma/drug therapy , Adrenal Cortex Hormones/therapeutic use , Cough , Dyspnea/drug therapy , Administration, Inhalation
7.
Jpn J Clin Oncol ; 54(5): 549-555, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38323655

ABSTRACT

BACKGROUND: Morphine is the most used opioid for dyspnea, but other opioids such as oxycodone and fentanyl are increasingly used, and opioid switching to these is sometimes undertaken. No studies have verified the effectiveness of opioid switching for relief of dyspnea. We retrospectively investigated the effectiveness of opioid switching for dyspnea and its predictors. METHODS: All patients with opioid switching for dyspnea during hospitalization at Komaki City Hospital from January 2019 to August 2022 were included. Opioid switching was defined as a change to another opioid, and the assessment period for evaluating the effectiveness and adverse events of opioid switching was set as 1 week. Patients with Numeric Rating Scale or Japanese version of the Support Team Assessment Schedule reduction for dyspnea of at least 1, or with clear improvement based on medical records, were considered valid. Mitigating factors for dyspnea were identified using logistic regression analysis. RESULTS: Of the 976 patients with opioid switching, 57 patients had opioid switching for relief of dyspnea. Of these, opioid switching was effective in 21 patients (36.8%). In a multivariate analysis, older patients (odds ratio: 5.52, 95% CI: 1.50-20.20, P < 0.01), short prognosis for post-opioid switching (odds ratio: 0.20, 95% CI: 0.04-0.87, P = 0.03) and cachexia (odds ratio: 0.12, 95% CI: 0.02-0.64, P < 0.01) were significantly associated with opioid switching effects for dyspnea. There were no serious adverse events after opioid switching. CONCLUSION: This study indicates that opioid switching for dyspnea may have some effect. Furthermore, opioid switching for dyspnea may be more effective in older patients and less effective in terminally ill patients or in those with cachexia.


Subject(s)
Analgesics, Opioid , Dyspnea , Neoplasms , Humans , Dyspnea/drug therapy , Dyspnea/etiology , Male , Retrospective Studies , Female , Analgesics, Opioid/therapeutic use , Analgesics, Opioid/administration & dosage , Aged , Neoplasms/complications , Neoplasms/drug therapy , Middle Aged , Aged, 80 and over , Drug Substitution , Fentanyl/administration & dosage , Fentanyl/therapeutic use
9.
Respir Med Res ; 85: 101082, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38280281

ABSTRACT

BACKGROUND: Dyspnea is a complex symptom of chronic obstructive pulmonary disease (COPD) which is not strongly correlated with lung function measures. Long-acting bronchodilators (LAB) may reduce this dyspnea, but some patients report persistent chronic dyspnea despite this treatment. This study aims to assess residual reversibility and clinical response after short-acting bronchodilator (SAB) in COPD patients already treated by LAB and reporting persistent dyspnea. METHODS: COPD patients with a persistent dyspnea (modified Medical Research Council scale (mMRC) ≥1) despite current stable treatment with at least one LAB were included. Spirometry, plethysmography and impulse oscillometry (IOS) were performed at peak effect of their LAB and repeat 45 min after the intake of two SAB (400 µg of salbutamol and 80 µg of ipratropium). Dyspnea improvement was assessed at 45 min after SAB through a comparative two-sided VAS (-100 mm for maximal improvement; +100 mm for maximal degradation). RESULTS: Twenty-two COPD patients were analyzed, mainly men (59.1 %) with a mean age of 60.6 years and a median FEV1 of 54 % of predicted values. Fifty percent of patients reported a severe basal dyspnea (mMRC ≥2). After SAB, spirometric and plethysmographic measurements were statistically improved. For IOS measurement, reactance at 5 Hz (X5) and area of reactance (AX) were also improved. Fifty percent of patients reported a clinically relevant improvement of their resting dyspnea. However, no correlation was found between dyspnea improvement and functional measures. CONCLUSIONS: Fifty percent of COPD patients regularly treated with one or two LAB still report a relevant improvement of resting dyspnea after the adjunctive intake of double short-acting bronchodilators. Physiological mechanisms associated with this improvement remain to be determined. CLINICAL TRIAL REGISTRATION: NCT02928744.


Subject(s)
Albuterol , Bronchodilator Agents , Dyspnea , Pulmonary Disease, Chronic Obstructive , Spirometry , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/therapeutic use , Male , Female , Middle Aged , Aged , Dyspnea/drug therapy , Dyspnea/etiology , Spirometry/methods , Albuterol/administration & dosage , Albuterol/therapeutic use , Oscillometry/methods , Treatment Outcome , Forced Expiratory Volume/drug effects , Plethysmography/methods , Ipratropium/administration & dosage , Ipratropium/therapeutic use
10.
BMJ Support Palliat Care ; 13(e3): e715-e729, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-37468224

ABSTRACT

INTRODUCTION: Although there is low-quality evidence, there has been an increase in publications on the experience of evaluating and managing cancer-related breathlessness using opioids other than morphine. METHODS: The author conducted a non-systematic literature review in the PubMed/Medline and Embase until 4 October 2022. Eligible studies have evaluated the efficacy of opioids other than morphine for cancer-related breathlessness. Studies focused on sedation, anaesthesia, paediatric patients, opioid toxicity or basic research were excluded. Reviews/meta-analyses and non-English language publications were also excluded. RESULTS: A total of 1556 records were identified, of which 23 studies including 469 patients who were treated with fentanyl (n=223), oxycodone (n=171) and hydromorphone (n=75) were considered eligible. Six phase II randomised clinical trials (RCTs), four observational studies and four case reports of fentanyl were found. For breathlessness on exertion, fentanyl yielded promising results, but no RCT showed significant superiority of fentanyl to placebo or morphine. For terminal breathlessness, three RCTs, five non-randomised or observational studies and one case report on oxycodone or hydromorphone were found. Although the results of the observational studies suggested that oxycodone and hydromorphone might be effective alternatives to morphine, the superiority over placebo or non-inferiority to morphine had not been demonstrated in the RCTs. CONCLUSION: As an alternative to morphine, the author recommends fentanyl for breathless crisis or breathlessness on exertion, and oxycodone or hydromorphone for terminal breathlessness in advanced cancer. Larger and well-designed studies based on firm research policies are needed to confirm this current knowledge.


Subject(s)
Analgesics, Opioid , Dyspnea , Neoplasms , Child , Humans , Analgesics, Opioid/therapeutic use , Dyspnea/drug therapy , Dyspnea/etiology , Fentanyl/therapeutic use , Hydromorphone/therapeutic use , Morphine , Neoplasms/complications , Oxycodone/therapeutic use
12.
Palliat Med ; 38(1): 156-162, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37978419

ABSTRACT

BACKGROUND: Chronic breathlessness adversely impacts people with chronic obstructive pulmonary disease and their caregivers (family and friends), who may, in turn, experience significant burden due to their caregiving role. Sustained-release morphine may reduce chronic breathlessness in some patients, which may have an impact on caregivers' perceived burden. AIM: To explore the impact on caregiver burden of active treatment of people with chronic breathlessness (modified Medical Research Council (mMRC) ⩾ 3) and chronic obstructive pulmonary disease (COPD) with regular, low-dose, sustained-release morphine within a multi-site, double-blind, randomised, placebo-controlled trial. DESIGN: Exploratory analysis of self-reported caregiver burden at baseline and end of week 3 in a randomised, double-blind, placebo-controlled study. Caregiver measures included: demographics and perceived burden (Zarit Burden Interview 12-item short-form questionnaire). Patient measures included: worst breathlessness and FitBitR-measures. SETTING/PARTICIPANTS: All consenting caregivers of trial patient participants in a multi-site study recruiting from palliative care and respiratory services. RESULTS: Caregivers (n = 49; 59% women; median age 68 years [IQR 50-75]) reported median baseline caregiver burden 12 [IQR 5-17], with 53% reporting high burden (⩾13). Eighty-four percent of caregivers reported no change in burden. In people whose worst breathlessness improved, caregiver burden moved in the same direction, though the correlation was not significant (rs = 0.25, p = 0.17). Conversely, caregiver burden worsened as patients' minutes lightly active increased, with the correlation being significant (rs = 0.56, p = 0.04). CONCLUSIONS: Caregivers reported high levels of caregiver burden, but patients' response to treatment in terms of their symptom and function may influence change in caregiver burden over a three-week period.


Subject(s)
Morphine , Pulmonary Disease, Chronic Obstructive , Aged , Female , Humans , Male , Middle Aged , Caregiver Burden , Caregivers , Delayed-Action Preparations/therapeutic use , Dyspnea/drug therapy , Morphine/therapeutic use , Double-Blind Method
13.
Ann Am Thorac Soc ; 21(1): 122-135, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37772975

ABSTRACT

Background: The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). Objective: To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with cyclophosphamide. Data Sources: A literature search was conducted across the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases through June 2022 for studies using cyclophosphamide to treat patients with SSc-ILD. Data Extraction: Mortality, disease progression, quality of life, and adverse event data were extracted, and meta-analyses were performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation Working Group method was used to assess the quality of evidence. Synthesis: Five studies were included; two randomized controlled trials compared cyclophosphamide versus placebo, and one randomized controlled trial and two retrospective case-control studies compared cyclophosphamide versus mycophenolate. Compared with placebo, there was a 2.83% reduction in the decline at 12 months for forced vital capacity (FVC) % predicted using cyclophosphamide (95% confidence interval [CI], 0.80-4.87; low evidence). There were improvements in breathlessness (Transition Dyspnea Index mean difference [MD], 2.90; 95% CI, 1.94-3.86; minimum clinically important difference, 1; moderate evidence) and disability (Health Assessment Questionnaire-Disability Index MD, -0.16; 95% CI, -0.28 to -0.04; minimum clinically important difference, -0.14; moderate evidence). There were increased risks of leukopenia and constitutional symptoms using cyclophosphamide, but no difference in mortality. When cyclophosphamide was compared with mycophenolate, there were differences in diffusing capacity of the lung for carbon monoxide % predicted favoring mycophenolate at 6 months (MD, -3.67%; 95% CI, -6.3% to -1.1% unadjusted; MD, -4.88%; 95% CI, -7.3% to -2.5% adjusted for alveolar volume; moderate evidence), 12 months (MD, -5.90%; 95% CI, -8.4% to -3.4% adjusted for alveolar volume; moderate evidence), and 18 months (MD, -3.26%; 95% CI, -6.1% to -0.4%; moderate evidence), but not at 24 months. There were no differences in FVC % predicted, mortality, or quality-of-life outcomes, but participants were more likely to prematurely discontinue cyclophosphamide compared with mycophenolate (relative risk, 1.70; 95% CI, 1.10-2.63; high-certainty evidence). Conclusions: A review of the published evidence shows that cyclophosphamide is effective in SSc-ILD compared with placebo, with an increased risk of side effects. However, mycophenolate may be equivocal or better than cyclophosphamide. Clinicians and patients should weigh the potential benefits and risks with respect to individual patient circumstances and preferences.


Subject(s)
Lung Diseases, Interstitial , Scleroderma, Systemic , Humans , Retrospective Studies , Quality of Life , Cyclophosphamide/therapeutic use , Immunosuppressive Agents/therapeutic use , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/complications , Dyspnea/drug therapy , Scleroderma, Systemic/complications , Scleroderma, Systemic/drug therapy
14.
J Ethnopharmacol ; 321: 117531, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38042387

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Zedoary turmeric oil injection (ZTOI) extracted from the rhizome extract of Curcuma phaeocaulis Valeton, Curcuma wenyujin Y. H. Chen et C. Ling or Curcuma kwangsiensis S. G. Lee et C. F. Liang, is widely used for the treatment of virus-induced upper respiratory tract infections, peptic ulcers, viral pneumonia, etc. However, it has attracted widespread attention because it often causes adverse drug reactions (ADRs), including dyspnea. However, little is known about the mechanism underlying dyspnea caused by ZTOI, which limits its clinical application. AIM OF THE STUDY: To investigate the major pathophysiologic signatures and underlying mechanism of ZTOI-related dyspnea. METHODS: Respiratory function detection was used to explore the pathophysiologic signature of dyspnea induced by ZTOI. UV-vis absorption spectroscopy and isothermal titration calorimetry were applied to test the interaction between ZTOI and hemoglobin (Hb). GC‒MS was used to identify the main components in ZTOI. Molecular docking, surface plasmon resonance, and circular dichroism spectroscopy were employed to test the reaction between ß-elemene and Hb. Western blot was performed to investigate the effect of ß-elemene on the hypoxia signaling pathway. RESULTS: The results showed that ZTOI-induced dyspnea was related to a decreased oxygen carrying capacity of Hb. The molecular interaction between ZTOI and Hb was proven. Notably, ß-elemene in ZTOI exhibited high binding affinity to Hb and altered its secondary structure. Furthermore, it was found that ß-elemene downregulated the expression of prolyl hydroxylase-domain protein 2 and upregulated the expression of hypoxia-inducible factor-1α. CONCLUSIONS: Our study is valuable for better understanding the pathophysiological characteristics and underlying mechanism of ZTOI to ensure its safe clinical application. We also provided a strategy to elucidate the underlying mechanism based on inspiration from clinical ADR phenotypes for investigating other medical products with ADRs in the clinic.


Subject(s)
Curcuma , Sesquiterpenes , Humans , Curcuma/chemistry , Hypoxia-Inducible Factor 1, alpha Subunit , Molecular Docking Simulation , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Hemoglobins , Dyspnea/chemically induced , Dyspnea/drug therapy
15.
Eur Respir J ; 63(2)2024 Feb.
Article in English | MEDLINE | ID: mdl-38135442

ABSTRACT

BACKGROUND: Dyspnoea and cough can have a profound impact on the lives of patients with pulmonary fibrosis. We investigated the effects of nintedanib on the symptoms and impact of pulmonary fibrosis in patients with progressive pulmonary fibrosis (PPF) in the INBUILD trial using the Living with Pulmonary Fibrosis (L-PF) questionnaire. METHODS: Patients had a fibrosing interstitial lung disease (ILD) (other than idiopathic pulmonary fibrosis) of >10% extent on high-resolution computed tomography (HRCT) and met criteria for ILD progression within the prior 24 months. Patients were randomised 1:1 to receive nintedanib or placebo. Changes in L-PF questionnaire scores from baseline to week 52 were assessed using mixed models for repeated measures. RESULTS: In total, 663 patients were treated. Compared with placebo, there were significantly smaller increases (worsenings) in adjusted mean L-PF questionnaire total (0.5 versus 5.1), symptoms (1.3 versus 5.3), dyspnoea (4.3 versus 7.8) and fatigue (0.7 versus 4.0) scores in the nintedanib group at week 52. L-PF questionnaire cough score decreased in the nintedanib group and increased in the placebo group (-1.8 versus 4.3). L-PF questionnaire impacts score decreased slightly in the nintedanib group and increased in the placebo group (-0.2 versus 4.6). Similar findings were observed in patients with a usual interstitial pneumonia-like fibrotic pattern on HRCT and in patients with other fibrotic patterns on HRCT. CONCLUSION: Based on changes in L-PF questionnaire scores, nintedanib reduced worsening of dyspnoea, fatigue and cough and the impacts of ILD over 52 weeks in patients with PPF.


Subject(s)
Idiopathic Pulmonary Fibrosis , Indoles , Lung Diseases, Interstitial , Humans , Vital Capacity , Disease Progression , Lung Diseases, Interstitial/drug therapy , Idiopathic Pulmonary Fibrosis/drug therapy , Fibrosis , Dyspnea/drug therapy , Cough/drug therapy , Double-Blind Method
16.
Cochrane Database Syst Rev ; 12: CD011600, 2023 12 06.
Article in English | MEDLINE | ID: mdl-38054551

ABSTRACT

BACKGROUND: Management of chronic obstructive pulmonary disease (COPD) commonly involves a combination of long-acting bronchodilators including beta2-agonists (LABA) and muscarinic antagonists (LAMA). LABA and LAMA bronchodilators are now available in single-combination inhalers. In individuals with persistent symptoms or frequent exacerbations, inhaled corticosteroids (ICS) are also used with combination LABA and LAMA inhalers. However, the benefits and risks of adding ICS to combination LABA/LAMA inhalers as a triple therapy remain unclear. OBJECTIVES: To assess the effects of adding an ICS to combination LABA/LAMA inhalers for the treatment of stable COPD. SEARCH METHODS: We searched the Cochrane Airways Group Register of Trials, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase up to 30 November 2022. We also searched ClinicalTrials.gov and the WHO ICTRP up to 30 November 2022. SELECTION CRITERIA: We included parallel-group randomised controlled trials of three weeks' duration or longer that compared the treatment of stable COPD with ICS in addition to combination LABA/LAMA inhalers against combination LABA/LAMA inhalers alone. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The primary outcomes were acute exacerbations of COPD, respiratory health-related quality of life, pneumonia and other serious adverse events. The secondary outcomes were symptom scores, lung function, physical capacity, and mortality. We used GRADE to assess certainty of evidence for studies that contributed data to our prespecified outcomes. MAIN RESULTS: Four studies with a total of 15,412 participants met the inclusion criteria. The mean age of study participants ranged from 64.4 to 65.3 years; the proportion of female participants ranged from 28% to 40%. Most participants had symptomatic COPD (COPD Assessment Test Score ≥ 10) with severe to very severe airflow limitation (forced expiratory volume in one second (FEV1) < 50% predicted) and one or more moderate-to-severe COPD exacerbations in the last 12 months. Trial medications differed amongst studies. The duration of follow-up was 52 weeks in three studies and 24 weeks in one study. We assessed the risk of selection, performance, and detection bias to be low in the included studies; one study was at high risk of attrition bias, and one study was at high risk of reporting bias. Triple therapy may reduce rates of moderate-to-severe COPD exacerbations compared to combination LABA/LAMA inhalers (rate ratio (RR) 0.74, 95% confidence interval (CI) 0.67 to 0.81; n = 15,397; low-certainty evidence). Subgroup analysis stratifying by blood eosinophil counts showed there may be a greater reduction in rate of moderate-to-severe COPD exacerbations with triple therapy in participants with high-eosinophils (RR 0.67, 95% CI 0.60 to 0.75) compared to low-eosinophils (RR 0.87, 95% CI 0.81 to 0.93) (test for subgroup differences: P < 0.01) (high/low cut-offs: 150 eosinophils/µL in three studies; 200 eosinophils/µL in one study). However, moderate-to-substantial heterogeneity was observed in both high- and low-eosinophil subgroups. These subgroup analyses are observational by nature and thus results should be interpreted with caution. Triple therapy may be associated with reduced rates of severe COPD exacerbations (RR 0.75, 95% CI 0.67 to 0.84; n = 14,131; low-certainty evidence). Triple therapy improved health-related quality of life assessed using the St George's Respiratory Questionnaire (SGRQ) by the minimal clinically important difference (MCID) threshold (4-point decrease) (35.3% versus 42.4%, odds ratio (OR) 1.35, 95% CI 1.26 to 1.45; n = 14,070; high-certainty evidence). Triple therapy may result in fewer symptoms measured using the Transition Dyspnoea Index (TDI) (OR 1.33, 95% CI 1.13 to 1.57; n = 3044; moderate-certainty evidence) and improved lung function as measured by change in trough FEV1 (mean difference 38.68 mL, 95% CI 22.58 to 54.77; n = 11,352; low-certainty evidence). However, these benefits fell below MCID thresholds for TDI (1-unit decrease) and trough FEV1 (100 mL), respectively. Triple therapy is probably associated with a higher risk of pneumonia as a serious adverse event compared to combination LABA/LAMA inhalers (3.3% versus 1.9%, OR 1.74, 95% CI 1.39 to 2.18; n = 15,412; moderate-certainty evidence). In contrast, all-cause serious adverse events may be similar between groups (19.7% versus 19.7%, OR 0.95, 95% CI 0.87 to 1.03; n = 15,412; low-certainty evidence). All-cause mortality may be lower with triple therapy (1.4% versus 2.0%, OR 0.70, 95% CI 0.54 to 0.90; n = 15,397; low-certainty evidence). AUTHORS' CONCLUSIONS: The available evidence suggests that triple therapy may reduce rates of COPD exacerbations (low-certainty evidence) and results in an improvement in health-related quality of life (high-certainty evidence) compared to combination LABA/LAMA inhalers, but probably confers an increased pneumonia risk as a serious adverse event (moderate-certainty evidence). Triple therapy probably improves respiratory symptoms and may improve lung function (moderate- and low-certainty evidence, respectively); however, these benefits do not appear to be clinically significant. Triple therapy may reduce the risk of all-cause mortality compared to combination LABA/LAMA inhalers (low-certainty evidence). The certainty of the evidence was downgraded most frequently for inconsistency or indirectness. Across the four included studies, there were important differences in inclusion criteria, trial medications, and duration of follow-up. Investigation of heterogeneity was limited due to the small number of included studies. We found limited data on the effects of triple therapy compared to combination LABA/LAMA inhalers in patients with mild-moderate COPD and those without a recent exacerbation history.


Subject(s)
Pneumonia , Pulmonary Disease, Chronic Obstructive , Humans , Female , Middle Aged , Aged , Muscarinic Antagonists , Bronchodilator Agents/therapeutic use , Adrenergic beta-2 Receptor Agonists/therapeutic use , Quality of Life , Pulmonary Disease, Chronic Obstructive/drug therapy , Adrenal Cortex Hormones/therapeutic use , Dyspnea/drug therapy , Pneumonia/drug therapy , Disease Progression
17.
Biosensors (Basel) ; 13(11)2023 Nov 13.
Article in English | MEDLINE | ID: mdl-37998160

ABSTRACT

Exercise increases the cost of breathing (COB) due to increased lung ventilation (V˙E), inducing respiratory muscles deoxygenation (∇SmO2), while the increase in workload implies ∇SmO2 in locomotor muscles. This phenomenon has been proposed as a leading cause of exercise intolerance, especially in clinical contexts. The use of high-flow nasal cannula (HFNC) during exercise routines in rehabilitation programs has gained significant interest because it is proposed as a therapeutic intervention for reducing symptoms associated with exercise intolerance, such as fatigue and dyspnea, assuming that HFNC could reduce exercise-induced ∇SmO2. SmO2 can be detected using optical wearable devices provided by near-infrared spectroscopy (NIRS) technology, which measures the changes in the amount of oxygen bound to chromophores (e.g., hemoglobin, myoglobin, cytochrome oxidase) at the target tissue level. We tested in a study with a cross-over design whether the muscular desaturation of m.vastus lateralis and m.intercostales during a high-intensity constant-load exercise can be reduced when it was supported with HFNC in non-physically active adults. Eighteen participants (nine women; age: 22 ± 2 years, weight: 65.1 ± 11.2 kg, height: 173.0 ± 5.8 cm, BMI: 21.6 ± 2.8 kg·m-2) were evaluated in a cycle ergometer (15 min, 70% maximum watts achieved in ergospirometry (V˙O2-peak)) breathing spontaneously (control, CTRL) or with HFNC support (HFNC; 50 L·min-1, fiO2: 21%, 30 °C), separated by seven days in randomized order. Two-way ANOVA tests analyzed the ∇SmO2 (m.intercostales and m.vastus lateralis), and changes in V˙E and ∇SmO2·V˙E-1. Dyspnea, leg fatigue, and effort level (RPE) were compared between trials by the Wilcoxon matched-paired signed rank test. We found that the interaction of factors (trial × exercise-time) was significant in ∇SmO2-m.intercostales, V˙E, and (∇SmO2-m.intercostales)/V˙E (p < 0.05, all) but not in ∇SmO2-m.vastus lateralis. ∇SmO2-m.intercostales was more pronounced in CTRL during exercise since 5' (p < 0.05). Hyperventilation was higher in CTRL since 10' (p < 0.05). The ∇SmO2·V˙E-1 decreased during exercise, being lowest in CTRL since 5'. Lower dyspnea was reported in HFNC, with no differences in leg fatigue and RPE. We concluded that wearable optical biosensors documented the beneficial effect of HFNC in COB due to lower respiratory ∇SmO2 induced by exercise. We suggest incorporating NIRS devices in rehabilitation programs to monitor physiological changes that can support the clinical impact of the therapeutic intervention implemented.


Subject(s)
Oxygen , Wearable Electronic Devices , Adult , Humans , Female , Young Adult , Cannula , Spectroscopy, Near-Infrared , Dyspnea/drug therapy , Muscles
18.
PLoS One ; 18(11): e0294357, 2023.
Article in English | MEDLINE | ID: mdl-37971989

ABSTRACT

During the COVID-19 pandemic, face masks on patients and healthy people have been recommended to prevent airborne transmission of the virus. This increased the number of people who felt stressed while wearing masks. In this study, we investigated the stress-relieving effects of attaching aroma seals to masks. A double-blind, randomized controlled trial was conducted involving 62 university students. The participants were randomly assigned to two groups and instructed to apply a seal to their masks once a day throughout the study period. The primary measure used was the Depression, Anxiety, and Stress Scale-21 (DASS-21), while the secondary measures included the assessment of breathlessness associated with mask-wearing and the World Health Organization Five Well-Being Index (WHO-5). The intervention group, referred to as the aroma-seal use group, utilized aroma seals infused with orange-lime essential oil with the expectation of experiencing the healing effects of citrus. On the other hand, the non-intervention group, known as the placebo-seal use group, utilized identical seals without any aroma. Results indicated that the aroma-seal use group exhibited significant improvements in both the total DASS-21 scores and depression scores compared to their baseline values by the second week of the intervention. Furthermore, the aroma-seal use group demonstrated a reduced occurrence of breathlessness while wearing masks compared to the placebo-seal group. Additionally, when assessing the item "I have felt calm and relaxed" from the WHO-5 questionnaire, the aroma-seal use group displayed significantly higher scores than the placebo group. Therefore, using aroma seals containing orange-lime essential oil could be beneficial in relieving mental stress and reducing breathlessness while wearing a mask, thus improving mental health.


Subject(s)
COVID-19 , Caniformia , Oils, Volatile , Seals, Earless , Humans , Animals , Odorants , Pandemics/prevention & control , COVID-19/prevention & control , Oils, Volatile/therapeutic use , Dyspnea/drug therapy
19.
Eur J Pharmacol ; 961: 176179, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37923161

ABSTRACT

AIMS: Dapagliflozin may confer additional decongestive and natriuretic benefits to patients with acute heart failure (AHF). Nonetheless, this hypothesis was not clinically examined. This study aimed primarily to investigate the effect of dapagliflozin on symptomatic relief in those patients. METHODS: This was a randomized, double-blind study that included 87 patients with AHF presenting with dyspnea. Within 24 h of admission, patients were randomized to receive either dapagliflozin (10 mg/day, N = 45) or placebo (N = 42) for 30 days. The primary outcome was the difference between the two groups in the area under the curve (AUC) of visual analogue scale (VAS) dyspnea score over the first 4 days. Secondary endpoints included urinary sodium (Na) after 2 h of randomization, percent change in NT-proBNP, cumulative urine output (UOP), and differences in mortality and hospital readmission rates. RESULTS: The results showed that dapagliflozin significantly reduced the AUC of VAS dyspnea score compared to placebo (3192.2 ± 1631.9 mm × h vs 4713.1 ± 1714.9 mm × h, P < 0.001). The relative change of NT-proBNP compared to its baseline was also larger with dapagliflozin (-34.89% vs -10.085%, P = 0.001). Additionally, higher cumulative UOP was found at day 4 (18600 ml in dapagliflozin vs 13700 in placebo, P = 0.031). Dapagliflozin decreased rehospitalization rates within 30 days after discharge, while it did not affect the spot urinary Na concentration, incidence of worsening of heart failure, or mortality rates. CONCLUSION: Dapagliflozin may provide symptomatic relief and improve diuresis in patients with AHF. Further studies are needed to confirm these findings. https://clinicaltrials.gov/study/NCT05406505.


Subject(s)
Heart Failure , Humans , Benzhydryl Compounds/therapeutic use , Dyspnea/drug therapy , Dyspnea/complications , Glucosides/therapeutic use , Heart Failure/complications , Stroke Volume , Double-Blind Method
20.
Postgrad Med ; 135(8): 784-802, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38032494

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality globally. In the major revision of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report, the scientific committee concluded that the use of long-acting ß2-agonist/inhaled corticosteroids (LABA/ICS) is not encouraged in patients with COPD. However, current prescribing patterns reveal significant use of LABA/ICS. In this paper, the evidence behind the current practice and the latest treatment recommendations is reviewed. We compare the efficacy and safety of combination therapy with long-acting muscarinic antagonist (LAMA) and LABA vs LABA/ICS and note that LAMA/LABA combinations have reduced the annual rate of moderate/severe exacerbations, delayed the time to first exacerbation, and increased post-dose FEV1 vs ICS-based regimens. The GOLD 2023 report recommends treatment with LABA and LAMA combination (preferably as a single inhaler) in patients with persistent dyspnea, with initiation of ICS in patients based on the symptoms (dyspnea and exercise intolerance as indicated by modified Medical Research Council [mMRC] score ≥ 2 and COPD Assessment Test [CAT™] > 20), blood eosinophil count (≥ 300 cells/µL), and exacerbation history (history of hospitalizations for exacerbations of COPD and ≥ 2 moderate exacerbations per year despite appropriate long-acting bronchodilator maintenance therapy). We describe practical recommendations for primary care physicians to optimize therapy for their patients and prevent overuse of ICS-based regimens. We advocate adherence to current recommendations and a greater focus on effective treatments to successfully control symptoms, minimize exacerbation risk, preserve lung function, maximize patient outcomes, and reduce the burden of drug-related adverse events.


Chronic obstructive pulmonary disease (COPD) is a common disease of the lungs associated with continued respiratory symptoms and airflow limitation. COPD causes symptoms such as breathlessness, cough, and production of phlegm, and, if not properly managed, these symptoms may get worse and result in flare-ups, also termed exacerbations. COPD management includes controlling symptoms while reducing the risk of exacerbations. COPD treatments include bronchodilators and inhaled corticosteroids (ICS). Bronchodilators help by widening the airways, making it easier to breathe. The two types of bronchodilators are long-acting muscarinic antagonists (LAMAs; these drugs prevent closing of the airways) and long-acting ß2-agonists (LABAs; these drugs relax the muscles around the airways to help keep the airways open for a longer time). ICS may reduce swelling in the airways in some patients with COPD. However, the use of ICS-based regimens as the first treatment choice has been linked to health risks and is not in keeping with the recent national and international recommendations. In this narrative review, we examine why the use of ICS-based regimens is still growing and explore, based on available evidence, and why this treatment course may not be optimal for most patients with COPD. We discuss how the treatment for COPD has changed over time, and our findings support the use of LAMA and LABA as the first course of therapy in many patients with COPD. We conclude that greater adherence to the treatment guidelines can help to improve treatment outcomes for many patients with COPD.


Subject(s)
Adrenergic beta-2 Receptor Agonists , Pulmonary Disease, Chronic Obstructive , Humans , Adrenergic beta-2 Receptor Agonists/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Muscarinic Antagonists/therapeutic use , Administration, Inhalation , Drug Therapy, Combination , Adrenal Cortex Hormones/therapeutic use , Dyspnea/chemically induced , Dyspnea/drug therapy , Bronchodilator Agents/therapeutic use
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