Mapping quality of life after balloon dilatation in subglottic stenosis using Dyspnea index and Short Form Health Survey-36.

PURPOSE: An accurate diagnosis and proper treatment plan are required to restore an adequate patent airway in fibrotic subglottic stenosis (SGS). Currently, the definitive treatment entails single-stage balloon dilatation with steroid injections. The primary aim was to evaluate successful airway restoration and general quality of life in cases with SGS in northern Sweden using robust patient reported outcomes. METHODS: All participants with need of surgical treatment due to SGS that had been referred to the department of otorhinolaryngology, University Hospital of Umeå from September 2020 to August 2023 was included. Exclusion criteria included malignant, extrathoracic or cartilaginous cause, age < 18 years, or incompetent to sign consent documents. We assessed the patient-reported outcome measures pre- as well as 3 months postoperatively. RESULTS: Of the 40 cases fulfilling the eligibility criteria's, 33 cases completed the Dyspnea index (DI) and the short form health survey (SF-36) pre- as well as 3 months post-operatively. Receiver operating characteristics showed significant improvement in DI as well as in SF 36 scores post-operatively. CONCLUSIONS: Evaluation of balloon dilatation in SGS in this cohort follow-up analysis shows clear improvement in patient quality of life using robust PROM 3 months postoperatively, ensuring the use of a safe and well-tolerated procedure.

How can we identify subglottic stenosis in patients with suspected obstructive disease?

PURPOSE: Subglottic stenosis, a rare condition of the upper airway, is frequently misdiagnosed as obstructive lung disease. The aim of this study was to investigate whether subglottic stenosis could be identified and distinguished from asthma and chronic obstructive pulmonary disease (COPD) using spirometry or the dyspnea index (DI). METHODS: The study population included 43 patients with asthma, 31 patients with COPD and 50 patients with subglottic stenosis planned to undergo endoscopic intervention. All patients completed the DI and underwent dynamic spirometry registering both inspiratory and expiratory volumes and flows, including the expiratory disproportion index (EDI), the ratio of forced expiratory volume in 1 s to peak expiratory flow. One-way analysis of variance assessed the discrepancy of the variables among the study groups, and receiver operating curve (ROC) analysis determined the measurement with the best discriminatory power providing a cutoff value, maximizing both sensitivity and specificity. RESULTS: The only statistically significant variables differing between all three groups were the EDI and the DI. The EDI showed an excellent area under the ROC curve (0.99, p < 0.001) with a cutoff value of 0.39 (98% sensitivity, 96% specificity), followed by DI (0.87, p < 0.001) with a cutoff score of > 25 (83% sensitivity and 78% specificity). CONCLUSION: In patients with dyspnea of unknown cause, an increase in EDI should arouse a suspicion of extrathoracic airway obstruction, advocating for further evaluation with laryngotracheoscopy.

Development and validation of the Exercise-Induced Laryngeal Obstruction Dyspnea Index (EILODI).

BACKGROUND: Exercise-induced laryngeal obstruction (EILO) causes exertional dyspnea and is important for its effect on quality of life, diagnostic confusion with exercise-induced asthma, and health care resource utilization. There is no validated patient-reported outcome measure specific to EILO. OBJECTIVE: We sought to develop, validate, and define a minimal clinically important difference for a patient-reported outcome measure to be used with adolescents and young adults with EILO. METHODS: A multidisciplinary group created a preliminary measure, modified by a 10-member participant focus group, with 20 items scored along a 5-point Likert scale. A subsequent cohort of participants recruited from a clinic, aged 12 to 21 years, with confirmed EILO by continuous laryngoscopy during exercise testing (1) completed the measure at 3 points in time over 28 days and (2) provided anchoring data in the form of a daily exercise log and categorical self-assessments of clinical improvement. Thirty additional participants without exertional dyspnea served as controls. RESULTS: Two hundred nineteen subjects with mild to severe EILO participated in the exploratory factor analysis, which identified 7 factors within the preliminary outcome measure. After a process of item reduction, a 12-item metric with a total score ranging from 0 to 48 was developed. Mean scores of patients with EILO and healthy controls at baseline were 28.8 ± 7.4 and 4.5 ± 7.4, respectively. A minimal clinically important difference of 6 was determined by comparison of index change with changes in categorical self-assessments of improvement. CONCLUSIONS: This is the first patient-reported outcome measure specifically designed for adolescents and young adults with EILO.

Dyspnea Index: An upper airway obstruction instrument; translation and validation in Swedish.

OBJECTIVE: Upper airway dyspnoea is a challenging condition in which assessing the discomfort experienced by the patient is essential. There are three patient-reported outcome (PRO) instruments developed particularly for this patient group, none of which is available in Swedish. The aim of this study was to translate the Dyspnea Index (DI) into Swedish and validate the instrument for use in the Swedish-speaking population by investigating its basic psychometric properties. DESIGN: A prospective instrument validation study. SETTING: Tertiary referral centre. PARTICIPANTS: Fifty-three (n = 53) patients with upper airway dyspnoea and 19 healthy controls. MAIN OUTCOME MEASURES: The questionnaire was translated into Swedish (swDI) with a forward-backward method. Reliability, repeatability, responsiveness and construct validity were assessed by asking the subjects to complete the swDI, a visual analog scale (VAS) at exertion and at rest and the Voice Handicap Index (VHI). RESULTS: The swDI showed excellent internal consistency (Cronbach's α: 0.85) and repeatability (interclass correlation coefficient: 0.87 and Pearson's r: .89) in the patient group. No ceiling effect was observed (maximum score achieved was 39; 85% of the patients scored ≤ 36). SwDI scores moderately correlated with VAS at exertion (r: .59) and at rest (r: .42), yet poorly with the VHI (r: .36). The effect size (ES) was 3.8. CONCLUSIONS: The swDI is a valid, robust and reliable questionnaire for self-assessment in Swedish-speaking patients with upper airway obstruction. A future anchor-based longitudinal study is needed to assess the smallest detectable change (SDC) and minimal important change (MIC) that were not estimated in our study.

Early Changes in eDiary COPD Symptoms Predict Clinically Relevant Treatment Response at 12 Weeks: Analysis from the CRYSTAL Study.

Early detection of treatment response is important in the long-term treatment and management of patients with chronic obstructive pulmonary disease (COPD). This analysis evaluated whether early improvement in symptoms, recorded in the first 7 or 14 days via an electronic diary (eDiary) compared with baseline, can predict clinically meaningful treatment responders at 12 weeks. CRYSTAL was a 12-week, randomized, open-label study that demonstrated the increased effectiveness of indacaterol/glycopyrronium (IND/GLY) or glycopyrronium (GLY), after a direct switch from on-going baseline therapies, in patients with symptomatic COPD and moderate airflow obstruction. The co-primary endpoints were trough forced expiratory volume in 1 second (FEV1) and transition dyspnea index (TDI) at Week 12. Patients' symptom status was recorded daily in an eDiary. Of 4,389 patients randomized, 3,936 and 3,855 reported symptoms on Days 7 and 14, respectively. Patients who reported an early decrease in symptoms on Day 7 or 14 were more likely to achieve the minimal clinically important difference of ≥100 mL in trough FEV1 or ≥ 1 point in TDI at Week 12. Using stepwise multivariate regression models we identified as best predictors of FEV1 responders the decrease in wheeze on Day 7, and nighttime symptoms and wheeze on Day 14; best predictors of TDI responders were decrease in nighttime symptoms and wheeze on Day 7, and nighttime symptoms, sputum and wheeze on Day 14. Early symptom improvement at Day 7 or 14, especially wheeze and nighttime symptoms, may identify patients with clinically important improvement in lung function and dyspnea at Week 12.

Long-Term Follow-up of 64 Patients With Idiopathic Subglottic Stenosis: Treatment Pathways, Outcomes, and Impact of Serial Intralesional Steroid Injections.

OBJECTIVE: To describe treatment pathways and long-term outcomes in 64 patients with idiopathic subglottic stenosis (iSGS), including the impact of serial intralesional steroid injection (SILSI) on degree of stenosis, need for subsequent operation, and patient-reported outcome measures. METHODS: Retrospective review of 64 female patients with iSGS undergoing varied management approaches, 57 of whom underwent SILSI as at least part of their care. Treatment pathways included SILSI only, endoscopic intervention followed by SILSI only, endoscopic interventions only, endoscopic intervention followed by SILSI followed by need for repeat endoscopic intervention, open surgery, and tracheotomy. Outcomes assessed included subjectively estimated percent airway stenosis, dyspnea index (DI), modified medical research council (MMRC) dyspnea scale, voice handicap index-10 (VHI-10), number of operative and office-based procedures performed, need for subsequent operative intervention, and inter-operative interval. RESULTS: Treatment pathways included SILSI alone (n = 6), endoscopic intervention(s) followed by SILSI only (n = 31), SILSI followed by additional endoscopic or office-based procedures (n = 16), open surgery (n = 3), and tracheostomy (n = 4). 57 of 64 patients underwent SILSI as at least part of their treatment. Inter-operative interval was increased after starting SILSI. Of patients undergoing SILSI, those with more procedures or shorter inter-operative interval prior to SILSI were more likely to return to the operating room. Estimated stenosis, DI, MMRC, and VHI-10 decreased with SILSI. Stenosis was not correlated with DI, MMRC, or VHI-10, though DI was correlated with both MMRC and VHI-10 score. CONCLUSION: Of 57 patients undergoing SILSI, 37 did not require further operative intervention. Improvements in inter-operative interval, dyspnea, and voice were observed across patients. Randomized trials to identify which patients may benefit most from SILSI are warranted.

Can the Remote Use of a Peak Flow Meter Predict Severity of Subglottic Stenosis and Surgical Timing?

OBJECTIVE: We aimed to assess the relationship between patient-performed and patient-reported peak flow meter (PFM) measurements with pulmonary function testing (PFT) and Dyspnea Index (DI) scores as a tool for monitoring Subglottic stenosis (SGS) disease progression remotely. METHODS: Thirty-five SGS patients were prospectively enrolled. Patients were given PFMs to report serial measurements from home. DI scores and PFT were recorded at serial clinic visits. Data were analyzed to determine the correlation between PFM measurements and PFT data. Pre-operative and post-operative PFM measurements, PFT, and DI scores were analyzed for patients who underwent operative intervention. Receiver operating characteristic (ROC) curves were created for PFM measurements, PFT data, and DI scores to predict the likelihood of surgery. RESULTS: PFM measurements had a "strong" correlation with the peak expiratory flow rate (PEFR), r = 0.78. Means of PEFR, PIFR, EDI, PFM measurements, and DI scores all significantly improved after the operative intervention (p ≤ 0.05). The area under the curve for ROC curves for DI scores, PFM measurements, and EDI were highest in our cohort with values of 0.896, 0.823, and 0.806, respectively. CONCLUSION: In our SGS cohort, PFM measurements correlate strongly with PEFR measurements. PFM measurements can adequately demonstrate disease progression and predict the need for surgery in this patient population. Together, DI scores and PFM measurements may be a useful tool to remotely follow patients with SGS and inform timing of in-person assessments. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:628-633, 2023.

Assessment of dyspnea in sarcoidosis using the Baseline Dyspnea Index (BDI) and the Transition Dyspnea Index (TDI).

INTRODUCTION: The Borg and Modified Medical Research Council (mMRC) dyspnea scales have been used to evaluate dyspnea in sarcoidosis. The Baseline Dyspnea Index (BDI) and Transitional Dyspnea Index (TDI) are useful for the assessment of dyspnea in COPD. It is not known if the BDI-TDI accurately assesses dyspnea in sarcoidosis patients. METHODS: Data was analyzed from the Registry for Advanced Sarcoidosis (ReAS), a multi-national database enrolling patients with advanced sarcoidosis and a comparison group of sarcoidosis patients with non-advanced disease. At baseline, patients completed a BDI questionnaire along with spirometry, 6-min walk distance (6MWD), mMRC, Borg score, fatigue assessment score (FAS) and HRQoL assessments using Kings Sarcoidosis Questionnaire (KSQ) and St Georges Respiratory Questionnaire (SGRQ). At 12-months, patients with advanced disease completed a TDI questionnaire along with the other measures. Correlations between BDI and baseline variables, and between TDI and changes in baseline variables were evaluated. RESULTS: There was significant correlation (p < 0.001 for all) between BDI and baseline 6MWD (rho = 0.336), FVC% (rho = 0.387), FEV1% (rho = 0.285), DLCO% (rho = 0.355), mMRC (rho = -0.721), Borg score (rho = -0.389), FAS (rho = -0.669), SGRQ (rho = -0.785), and KSQ (rho = 0.318 to 0.724). At follow-up, TDI correlated with BDI, but not with changes in pulmonary function or other dyspnea measures. CONCLUSION: BDI scores correlated with pulmonary function, 6MWD, and other dyspnea measures. TDI scores did not correlate with changes in pulmonary function or other dyspnea measures. BDI may be a useful independent measure of dyspnea in sarcoidosis patients. The role of TDI needs further evaluation in longitudinal studies associated with changes in clinical parameters.

Effect of Medialization on Dyspnea Index in Unilateral Vocal Fold Paralysis.

OBJECTIVE: Patients with unilateral vocal fold paralysis commonly report dysphonia and dysphagia. Dyspnea also occurs, with studies on treatment-related change producing mixed results. Studies including patient-reported outcomes have focused on single-question global scales. The Dyspnea Index (DI) includes 10 questions, is specific to upper airway-related dyspnea, and may better capture these patients' symptoms. We evaluated change in DI after treatment. STUDY DESIGN: Retrospective review. SETTING: Academic medical center. METHODS: Forty-three patients with unilateral vocal fold paralysis underwent injection augmentation (n = 25) or framework surgery (n = 18). DI was recorded preprocedure, 2 to 4 weeks afterward, and at approximately 3 months afterward in 19 patients. Voice Handicap Index-10, Glottal Function Index, Cough Severity Index, and Eating Assessment Tool-10 were also recorded. Change in parameters and correlations were assessed. Obesity, cardiac disease, pulmonary disease, and procedure (injection vs framework surgery) were evaluated for effect on DI. RESULTS: Twenty-four patients had an abnormal baseline DI (>10). DI decreased from 14.9 ± 13.8 to 6.5 ± 9.3 after treatment (P < .001; 95% CI, 4.7-12.1). Twenty-eight scores decreased, 9 remained unchanged, and 6 increased. Change in DI was influenced by the presence of cardiac disease. Decreased DI persisted at 3-month follow-up. Voice Handicap Index-10, Glottal Function Index, Cough Severity Index, and Eating Assessment Tool-10 scores decreased and were correlated with change in DI. CONCLUSION: Upper airway-related dyspnea is common in unilateral vocal fold paralysis, occurring in half of this cohort. Correcting glottic insufficiency may alleviate symptoms. Treatment decision making should consider postprocedural change in dyspnea, especially in patients for whom dyspnea is a motivating factor for seeking treatment.

Monitoring Adult Subglottic Stenosis With Spirometry and Dyspnea Index: A Novel Approach.

OBJECTIVE: The aim was to examine the correlations among the anatomic Cotton-Myer classification, pulmonary function tests (PFTs), and patient-perceived dyspnea or dysphonia in patients with subglottic stenosis and identify measurements accurately reflecting treatment effects. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. METHOD: Fifty-two adults receiving endoscopic treatment for isolated subglottic stenosis were consecutively included. Correlations were calculated among the preoperative Cotton-Myer scale, PFTs, the Dyspnea Index (DI), and the Voice Handicap Index. Receiver operating characteristic curves were determined for PFT, DI, and Voice Handicap Index pre- and postoperative measurements. RESULTS: The Cotton-Myer classification correlated weakly with peak expiratory flow (r = -0.35, P = .012), expiratory disproportion index (r = 0.32, P = .022), peak inspiratory flow (r = -0.32, P = .022), and total peak flow (r = -0.36, P = .01). The DI showed an excellent area under the curve (0.99, P < .001), and among PFTs, the expiratory disproportion index demonstrated the best area under the curve (0.89, P < .001), followed by total peak flow (0.88, P < .001), peak expiratory flow (0.87, P < .001), and peak inspiratory flow (0.84, P < .001). Patients treated endoscopically with balloon dilatation showed a 53% decrease in expiratory disproportion index (95% CI, 41%-66%; P < .001) and a 37% improvement in peak expiratory flow (95% CI, 31%-43%; P < .001). CONCLUSION: Expiratory disproportion index or peak expiratory flow combined with DI was a feasible measurement for the monitoring of adult subglottic stenosis. The percentage deterioration of peak expiratory flow and increase in expiratory disproportion index correlated significantly with a proportional percentage increase in DI.

Adjunctive Inspiratory Muscle Training During a Rehabilitation Program in Patients With Breast Cancer: An Exploratory Double-Blind, Randomized, Controlled Pilot Study.

Objective: To investigate whether inspiratory muscle training (IMT) offered adjunctively to an exercise training program reduces symptoms of dyspnea in survivors of breast cancer. Design: Double-blind, parallel-group, randomized controlled trial. Setting: Outpatient rehabilitation program in a university hospital. Participants: Ninety-eight female patients with breast cancer who completed adjuvant treatment and subsequently entered cancer rehabilitation were screened for participation. Inclusion criteria were reduced inspiratory muscle strength and/or symptoms of dyspnea. Twenty patients (N=20) were randomly assigned to an intervention group (n=10) or a control group (n=10). Intervention: Both groups received a 3-month exercise training program in combination with either IMT (intervention) or sham-IMT (control). Main Outcome Measures: Changes in dyspnea intensity perception (10-point Borg Scale) at comparable time points (isotime) during constant work rate cycling was the primary outcome. Secondary outcomes included changes in respiratory muscle function, exercise capacity, and changes in symptoms of dyspnea during daily life (Transitional Dyspnea Index [TDI]). Results: The intervention group achieved a larger reduction in exertional dyspnea at isotime compared with the control group (-1.8 points; 95% CI, -3.7 to 0.13; P=.066). The intervention group also exhibited larger improvements in dyspnea during daily life (TDI score, +2.9 points; 95% CI, 0.5-5.3; P=.022) and improved both respiratory muscle endurance (+472 seconds; 95% CI, 217-728; P=.001) and cycling endurance (+428 seconds; 95% CI, 223-633; P=.001) more than the control group. Conclusions: Because of the limited sample size all obtained findings need to be interpreted with caution. The study offers initial insights into the potential of adjunctive IMT in selected survivors of breast cancer. Larger multicenter studies should be performed to further explore the potential role and general acceptance of this intervention as a rehabilitation tool in selected patients after breast cancer treatment.

The Reliability of the Arabic Version of the Dyspnea Index Questionnaire for Upper Airway-Related Dyspnea.

Objectives This study aimed to translate the Dyspnea Index (DI) questionnaire into the Arabic language and determine whether this version is valid and reliable for Arabic-speaking patients with upper airway-related dyspnea. Methods A cross-sectional study was conducted at the King Saud University Medical City otolaryngology clinics in Riyadh, Saudi Arabia. The DI questionnaire was translated into Arabic and then back-translated into the English language. Inclusion criteria were preoperative patients presenting to the otolaryngology clinic with upper airway-related dyspnea between November and December 2020. The results of internal consistency and factor analysis among the items were compared to the original DI development results to assess the reliability of the questionnaire. Results Among a total of 57 recruited patients, 50 questionnaires were completed with an 88% response rate. The mean age of the included patients was 38 ±14 years. Women constituted 58% of the patients. The most common diagnosis was subglottic stenosis (72%). Principle component extraction in factor analysis revealed a single underlying factor for all the questions. Factor loading ranged from 0.69 to 0.85. Reliability statistics showed a high value of internal consistency among the items. The mean inter-item correlation was 0.58. Conclusion Based on our findings, the Arabic version of the DI questionnaire is a reliable instrument for evaluating upper airway dyspnea.

Validity of the Modified Dyspnea Index for the French-Canadian Population.

BACKGROUND AND PURPOSE: Multidimensional tools could evaluate the dyspnea of patients with chronic lung disease. The aim was to validate the use of the French-Canadian version of the modified dyspnea index (MDI) among patients with pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). METHODS: The Spearman test analyzed the convergent validation of the MDI with pulmonary function tests (PFTs), New York Heart Association (NYHA) functional classification, the Modified Borg Scale, the Veterans Specific Activity Questionnaire (VSAQ), physical capacity, physical activity (Godin-Shephard Leisure-Time Physical Activity Questionnaire [GSLTPAQ]), and quality of life (SF-12). RESULTS: The MDI had a low correlation with PFT and physical activity; a moderate with physical capacity; a high with the physical dimension (SF-12). CONCLUSION: The results support the convergent validation of the MDI French-Canadian version with PAH or ILD.

Comparison between tools for measuring breathlessness: Cross-sectional validation of the Japanese version of the Dyspnoea-12.

INTRODUCTION: The Dyspnoea-12 (D-12) is a brief, easy to complete questionnaire for measuring breathlessness. OBJECTIVES: To facilitate further efforts to measure dyspnoea in real clinical settings, the authors aimed to develop and validate a Japanese version of the D-12 and also compare the D-12 with the Baseline Dyspnea Index (BDI) and the Activity component of the St. George's Respiratory Questionnaire (SGRQ). METHODS: The standardized procedure in accordance with international guidelines was used to create the translation. A validation study with a cross-sectional observational design was conducted on 122 subjects with stable chronic obstructive pulmonary disease (COPD). RESULTS: The internal consistency of the D-12 was high (Cronbach's coefficient α = 0.883) and similar to that of the BDI (α = 0.824) and SGRQ Activity (α = 0.872). The relationships between tools were statistically significant (|Rs | = 0.53 to 0.66). Although the scores obtained from all three tools were skewed toward the milder end of the respective scales, this deviation was most prominent in the D-12 with a floor effect of 48.4%. CONCLUSION: The Japanese version of the D-12 was successfully validated, but we should be careful of any floor effect and marked skew to the mild end of the scale, especially in subjects with mild COPD.

Office-Based Steroid Injections for Idiopathic Subglottic Stenosis: Patient-Reported Outcomes, Effect on Stenosis, and Side Effects.

OBJECTIVE: Office-based steroid injection has shown promise for idiopathic subglottic stenosis (iSGS). It is important to understand safety and patient-lived experience. We report patient experience related to airway restriction, voice, and side effects. METHODS: Sixteen patients (51 ± 14 years) with mild-moderate (20-50%) stenosis undergoing office-based transnasal steroid injections were included; fourteen had prior operations. Patients typically underwent three injections, 1 month apart, followed by transnasal tracheoscopy 1 month later to evaluate outcome; number of injections can vary based on disease severity and response. Outcomes were Dyspnea Index (DI), Modified Medical Research Council (MMRC) dyspnea scale, voice handicap index-10 (VHI-10), and degree of stenosis (estimated from procedural video). At each visit, patients were queried about post-injection airway restriction and side effects. Paired t-tests compared values at baseline versus follow-up tracheoscopy. RESULTS: DI decreased (t = 3.938, P = 0.0013), as did MMRC (t = 2.179, P = 0.0457). There was no change in VHI-10 (t = 1.354; P = 0.1957) scores. Airway stenosis decreased (t = 4.331; P = 0.0006); this was not correlated with change in DI (r = 0.267, P = 0.318). Side effects included airway restriction lasting <48 hours (n = 5), cough (n = 3), and nasal pain (n = 2). CONCLUSION: Steroid injections improved upper airway symptoms. Side effects were mild and transient. Improvement in DI did not correlate with percent stenosis.

Efficacy and Safety of Once-Daily Inhaled Umeclidinium in Asian Patients with COPD: Results from a Randomized, Placebo-Controlled Study.

Purpose: Previous studies demonstrating efficacy and safety of once-daily umeclidinium (UMEC) in patients with chronic obstructive pulmonary disease (COPD) have included few Asian patients. This study evaluated efficacy and safety of UMEC 62.5 mcg versus placebo in Asian patients with COPD. Patients and Methods: A Phase III, randomized, double-blind, parallel-group study. Patients (aged ≥40 years with COPD, pre-, and post-albuterol forced expiratory volume in 1 s [FEV1]/forced vital capacity ratio <0.70 and low risk of exacerbations) were randomized 2:1 to once-daily UMEC 62.5 mcg or placebo via the ELLIPTA inhaler for 24 weeks. Primary endpoint was change from baseline (CFB) in trough FEV1 on Day 169. Secondary endpoints were weighted mean FEV1 over 0-6 hrs post-dose on Day 1 and CFB in Transition Dyspnea Index (TDI) focal score on Day 168. Results: A total of 306 patients were included in the modified intent-to-treat population (UMEC: 205; placebo: 101). UMEC versus placebo provided a statistically significant improvement in least squares (LS) mean trough FEV1 between baseline and Day 169 (154 mL [95% confidence interval (CI): 113, 194]; p<0.001). A clinically meaningful difference of 125 mL in favor of UMEC (95% CI: 103, 147; p<0.001) was also seen in LS weighted mean FEV1 0-6 hrs post-dose on Day 1. A LS mean treatment difference in TDI focal score of 0.9 units in favor of UMEC was seen on Day 168 (95% CI: 0.3, 1.5; p=0.004). Incidence of on-treatment adverse events (AEs) was lower in the placebo (55%) versus UMEC arm (60%); non-fatal serious AEs, drug-related AEs, and AEs leading to withdrawal were similar with UMEC and placebo. Conclusion: Once-daily UMEC 62.5 mcg resulted in statistically significant and clinically meaningful improvements in lung function and dyspnea, compared with placebo, in Asian patients with COPD, with no new safety concerns observed.

The Role of Spirometry and Dyspnea Index in the Management of Subglottic Stenosis.

OBJECTIVES: We aimed to assess the role of spirometry measures and Dyspnea Index (DI) in response to treatment of subglottic stenosis (SGS) and ability to predict need for surgery. We also assessed correlations between spirometry measures, DI, and physical SGS parameters. METHODS: Thirty-seven adult female SGS patients were prospectively enrolled. Spirometry data and DI were obtained at serial clinic visits; physical SGS parameters were obtained intraoperatively. PIFR, PEFR, EDI, FEV1/FVC, and DI were compared preoperatively to postoperatively for patients who underwent operative intervention. Spirometry data, DI, and physical SGS parameters were analyzed for correlations, and receiver operating characteristic (ROC) curves were created for spirometry measures and DI to determine optimal cutoffs for recommending surgery. RESULTS: Means of all measured spirometry measures changed significantly from preoperative to postoperative visits (P < .05). Mean DIs changed significantly between preoperative (27.5, n = 13, SD = 8.6) and postoperative visits (8.6, n = 13, SD = 5.5, P < 5 × 10-5 ). All Pearson correlations were negligible to moderate. The area under the curve (AUC) for peak inspiratory flow rate (PIFR) was 0.903 (95% CI, 0.832-0.974) with cutoff at 2.10 L/s; the AUC for DI was 0.874 (95% CI, 0.791-0.956) with cutoff between 22-25; the AUC for peak expiratory flow rate (PEFR) was 0.806 (95% CI, 0.702-0.910) with cutoff at 2.5 L/s; all other ROC curves were less than good. CONCLUSION: PIFR, PEFR, EDI, FEV1/FVC, and DIs significantly improve after treatment for SGS. No strong correlations exist between spirometry measures, DI, and physical SGS parameters. PIFR was the most sensitive and specific for predicting timing of operative intervention in our cohort. LEVEL OF EVIDENCE: 1b Laryngoscope, 2019.

The Impact of Twice-Daily Indacaterol/Glycopyrrolate on the Components of Health-Related Quality of Life and Dyspnea in Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic cough, dyspnea, and excessive sputum production, the characteristic symptoms of chronic obstructive pulmonary disease (COPD), can negatively affect patients' health-related quality of life (HRQoL). The fixed-dose combination of a long-acting beta2-adrenergic agonist and a long-acting muscarinic antagonist (LABA/LAMA) have been shown to improve HRQoL and COPD symptoms as measured by the St George's Respiratory Questionnaire (SGRQ) and the Transition Dyspnea Index (TDI) total scores. However, the impact of a LABA/LAMA on the individual components of HRQoL and dyspnea with daily activities is unknown. METHODS: Secondary analysis of pooled data from 2 replicate, phase 3, 12-week, randomized, placebo, and active-controlled trials of twice-daily indacaterol/glycopyrrolate (IND/GLY) were analyzed. Change from baseline in HRQoL and dyspnea was measured by SGRQ and TDI, respectively. Total and component scores were evaluated using linear mixed models. Logistic regression was used to analyze the proportion of patients achieving minimum clinically important difference. Study outcomes were further explored in patient subgroups. RESULTS: A total of 2038 patients from FLIGHT1/FLIGHT2 studies were evaluated. IND/GLY significantly improved SGRQ component scores (symptoms [-7.3], activity [-3.6], and impacts [-5.0]); all P < 0.001 compared with placebo. IND/GLY also significantly improved symptoms scores compared with IND and GLY (-3.5 and -3.7, respectively; both P < 0.001). Patients treated with IND/GLY also had significant improvements in TDI component scores compared with placebo: functional impairment (0.48), magnitude of task (0.61), and magnitude of effort (0.54); all P < 0.001. All component scores were significantly higher for IND/GLY compared with IND and GLY (P ≤ 0.002 for all). CONCLUSIONS: Twice-daily IND/GLY significantly improved total scores as well as components of HRQoL and dyspnea in patients with COPD. These data demonstrate multiple clinical benefits of LABA/LAMA maintenance therapy in the COPD population. ClinicalTrials.gov: NCT01727141 and NCT01712516.

Healthcare Professionals' Preferred Efficacy Endpoints and Minimal Clinically Important Differences in the Assessment of New Medicines for Chronic Obstructive Pulmonary Disease.

BACKGROUND: Registration authorities evaluate effects of new medicines for chronic obstructive pulmonary disease (COPD) on airway obstruction, dyspnea, health status and exacerbations. To establish clinical relevance, minimal clinically important differences (MCIDs) are used. The aim of this study was to investigate which efficacy endpoints and MCIDs healthcare professionals consider clinically relevant for new COPD medicines. MATERIALS AND METHODS: 7,731 Healthcare professionals received an electronic questionnaire. Participants were asked for: 1) preferred efficacy endpoints for new COPD medicines and 2) cut-off values defining clinical relevance for forced expiratory volume in 1 sec (FEV1), Transition Dyspnea Index (TDI) and St. George's Respiratory Questionnaire (SGRQ). Those cut-off values were compared to the MCIDs used by registration authorities, namely 100 ml for FEV1, 1 unit for TDI and 4 units for SGRQ. RESULTS: 227 Healthcare professionals responded to the questionnaire. Most preferred efficacy endpoints were exacerbations (51.0%), airway obstruction (46.9%) and health status (44.9%). Mean cut-off values for TDI and SGRQ were significantly higher than the corresponding MCIDs, mean differences 1.5 (95%CI = 1.3-1.8, p < 0.001) and 7.0 (95%CI = 5.1-8.8, p < 0.001), respectively. The mean cut-off value for FEV1 was comparable to the MCID (mean difference 2.2, 95%CI = -19.9-24.3, p = 0.84). CONCLUSIONS: Healthcare professionals largely agree with efficacy endpoints used for the evaluation of new COPD medicines. However, they seem to prefer higher cut-off values for clinical relevance for TDI and SGRQ than the registration authorities. Effects of new medicines on TDI and SGRQ that are considered clinically relevant by registration authorities do, therefore, not necessarily reflect healthcare professionals' perspectives on clinical relevance.

Indacaterol/glycopyrronium reduces the risk of clinically important deterioration after direct switch from baseline therapies in patients with moderate COPD: a post hoc analysis of the CRYSTAL study.

PURPOSE: COPD is a progressive disease characterized by exacerbations and a decline in health status and lung function. Clinically important deterioration (CID) is a composite endpoint used to evaluate treatment efficacy. This analysis evaluated the impact of a direct switch to once-daily indacaterol/glycopyrronium 110/50 µg (IND/GLY) from previous monotherapy with a long-acting ß2-agonist (LABA) or long-acting muscarinic antagonist (LAMA) or with an LABA and an inhaled corticosteroid (LABA + ICS) on reducing CID. METHODS: CRYSTAL was a 12-week, prospective, multicenter, randomized, open-label study conducted in clinical practice settings. Three definitions of CID (D1-D3) were used, including: 1) ≥100 mL decrease in trough forced expiratory volume in 1 second (FEV1), 2) ≥1 point decrease in transition dyspnea index (TDI) and/or ≥0.4 points increase in clinical COPD questionnaire score (CCQ), or 3) an acute moderate/severe exacerbation (AECOPD). In D1 and D2, either TDI or CCQ was evaluated along with FEV1 and AECOPD, whereas in D3, all 4 parameters were included. ClinicalTrials.gov number: NCT01985334. RESULTS: Of the 2,159 patients analyzed, 1,622 switched to IND/GLY and 537 continued their baseline treatments. The percentage of patients with a CID was significantly lower after a direct switch to IND/GLY versus LABA or LAMA using all 3 CID definitions (D1: odds ratio [OR] 0.41 [95% CI: 0.30-0.55]; D2: OR 0.41 [95% CI: 0.31-0.55]; D3: OR 0.39 [95% CI: 0.29-0.52]). Compared with LABA + ICS, IND/GLY also reduced the risk of CID (D1: OR 0.76 [95% CI: 0.56-1.02]; D2: OR 0.75 [95% CI: 0.56-1.00]; D3: OR 0.67 [95% CI: 0.51-0.89]). CONCLUSION: In this analysis, IND/GLY reduced the risk of a CID in moderate COPD patients after direct switch from LABA + ICS or LABA or LAMA in real-life clinical practice.