Cough Response to High-Dose Inhaled Corticosteroids in Patients with Chronic Cough and Fractional Exhaled Nitric Oxide Levels ≥ 25 ppb: A Prospective Study.

This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25 ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4 years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.

Association of Cough Severity with Asthma Control and Quality of Life in Patients with Severe Asthma.

PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.

Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study.

PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.

Baseline Cohort Profile of the Korean Chronic Cough Registry: A Multicenter, Prospective, Observational Study.

PURPOSE: The Korean Chronic Cough Registry study was initiated to characterize patients with chronic cough (CC) and investigate their outcomes in real-world clinical practice. This report aims to describe the baseline cohort profile and study protocols. METHODS: This multicenter, prospective observational cohort study included newly referred CC patients and those already being treated for refractory or unexplained chronic cough (RUCC). Cough status was assessed using a visual analog scale, the Leicester Cough Questionnaire (LCQ), and the Cough Hypersensitivity Questionnaire (CHQ). RESULTS: A total of 610 patients (66.9% women; median age 59.0 years) were recruited from 18 centers, with 176 being RUCC patients (28.9%). The median age at CC onset was 50.1 years, and 94.4% had adult-onset CC (≥ 19 years). The median cough duration was 4 years. Compared to newly referred CC patients, RUCC patients had a longer cough duration (6.0 years vs. 3.0 years) but had fewer symptoms and signs suggesting asthma, rhinosinusitis, or gastroesophageal acid reflux disease. Subjects with RUCC had lower LCQ scores (10.3 ± 3.3 vs. 11.6 ± 3.6; P < 0.001) and higher CHQ scores (9.1 ± 3.9 vs. 8.4 ± 4.1; P = 0.024). There were no marked differences in the characteristics of cough between refractory chronic cough and unexplained chronic cough. CONCLUSIONS: Chronic cough typically develops in adulthood, lasting for years. Cough severity and quality of life impairment indicate the presence of unmet clinical needs and insufficient cough control in real-world clinical practice. Longitudinal follow-up is warranted to investigate the natural history and treatment outcomes.

Effectiveness and Safety of Codeine and Levodropropizine in Patients With Chronic Cough.

BACKGROUND: Recent progress in chronic cough management includes controlling cough triggers and hypersensitivity using antitussives. Therefore, we investigated the effects and safety outcomes of antitussives, codeine and levodropropizine, in patients with chronic cough. METHODS: We conducted an open-label, randomized comparative trial with newly referred patients with chronic cough. Patients were orally administered codeine (60 mg/day) and levodropropizine (180 mg/day) for 2 weeks. Cough severity, including the visual analog scale (VAS), Cough Symptom Score (CSS), Leicester Cough Questionnaire (LCQ), and safety for each treatment were assessed. The primary outcome was VAS score changes before and after 2 weeks of treatment. RESULTS: Among the 88 participants, 45 and 43 in the codeine and levodropropizine groups, respectively, were included in the analysis. Changes in the VAS score were higher in the codeine group than in the levodropropizine group (35.11 ± 20.74 vs. 19.77 ± 24.83, P = 0.002). Patients administered codeine also had improved CSS (2.96 ± 2.35 vs. 1.26 ± 1.89, P < 0.001) and LCQ (3.28 ± 3.36 vs. 1.61 ± 3.53, P = 0.025) than those administered levodropropizine. Treatment-related adverse events, including drowsiness, constipation, and headaches, were more frequent in the codeine group than in the levodropropizine group. However, no significant differences existed in the adverse events leading to discontinuation. CONCLUSION: Codeine is an effective and generally well-tolerated antitussive for chronic cough. However, it may induce side effects in some patients. Individual responses and adverse events should be carefully monitored when codeine is used to treat chronic cough.

The lung microbiota in Korean patients with non-tuberculous mycobacterial pulmonary disease.

BACKGROUND: The microbiota of the lower respiratory tract in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) has not been fully evaluated. We explored the role of the lung microbiota in NTM-PD by analyzing protected specimen brushing (PSB) and bronchial washing samples from patients with NTM-PD obtained using a flexible bronchoscope. RESULTS: Bronchial washing and PSB samples from the NTM-PD group tended to have fewer OTUs and lower Chao1 richness values compared with those from the control group. In both bronchial washing and PSB samples, beta diversity was significantly lower in the NTM-PD group than in the control group (P = 2.25E-6 and P = 4.13E-4, respectively). Principal component analysis showed that the PSBs and bronchial washings exhibited similar patterns within each group but differed between the two groups. The volcano plots indicated differences in several phyla and genera between the two groups. CONCLUSIONS: The lower respiratory tract of patients with NTM-PD has a unique microbiota distribution that is low in richness/diversity.

The impact of life behavior and environment on particulate matter in chronic obstructive pulmonary disease.

BACKGROUND: The effect of exposure to particulate matter (PM) on human health is a global public health concern. To develop an effective strategy to reduce PM exposure, we performed detailed questionnaire surveys regarding the type of lifestyle required to avoid PM exposure in patients with chronic obstructive pulmonary disease (COPD). We correlated the data with real-time PM concentration during the winter season. METHODS: We enrolled 104 patients with COPD aged 40 years or older. Detailed questionnaire surveys were conducted among participants, and internet of things-based sensors were installed at their homes to measure the indoor PM2.5 concentration, which was continuously monitored between December 2019 and February 2020. The associations among PM2.5 concentration, patients' lifestyles, and the impact of both concentration and lifestyle on COPD exacerbation were analyzed. RESULTS: Mean outdoor PM2.5 concentration was higher than mean indoor PM2.5 concentration during the study period (21.28 ± 5.09 µg/m3 vs. 12.75 ± 7.64 µg/m3), with a mean difference of 8.53 ± 7.99 µg/m3. Among the various social factors and practices that aim to avoid exposure to PM, six practices and economic statuses were confirmed to reduce indoor PM2.5 concentration compared to outdoor concentration; Contrarily, these practices created a significant difference between the outdoor and indoor PM2.5 concentrations. The six practice items that showed a significant difference were 1) checking air quality forecast (the difference: -13.31 ± 1.35 µg/m3, p = 0.013), 2) indoor air filter operated (-15.43 ± 1.32 µg/m3, p < 0.001), 3) ventilating home by opening the windows (-13.14 ± 1.28 µg/m3, p = 0.013), 4) checking filters of the air filter (-13.95 ± 1.50 µg/m3, p = 0.002), 5) refraining from going out when outside PM is high (-12.52 ± 1.37 µg/m3, p = 0.039), 6) wearing a mask when going out (-13.38 ± 1.32 µg/m3, p = 0.017). The higher the household income and economic level, the more significant the difference in the PM2.5 concentration. Severe exacerbation was more prevalent among patients with acute exacerbation as the exposure time of PM2.5≥35 µg/m3 or PM2.5≥75 µg/m3. CONCLUSION: Lifestyle and economic levels can affect the indoor PM2.5 concentration, which may impact COPD exacerbation.

Prevalence and diagnostic values of laboratory animal allergy among research personnel.

BACKGROUND: Laboratory animal allergy (LAA) has not been sufficiently investigated, although LAA is a relatively common work-related condition and important occupational hazard. OBJECTIVE: This study aimed to evaluate the prevalence of LAA and analyze the diagnostic value of serum specific IgE (sIgE) using the skin prick test (SPT) as a comparative standard. METHODS: Korean laboratory animal researchers who attended an annual symposium were requested to answer questionnaires regarding demographic characteristics, laboratory animal exposure, and symptoms related to laboratory animal exposure. A total of 213 participants underwent a SPT with mouse and rat epithelial allergen extract. We measured sIgE against rodent urine, epithelium, and serum allergens from 63 participants. SPT outcome served as the comparison method. RESULTS: Among 223 participants, 213 had direct/indirect exposure to mice or rats, and 30% and 14% of them complained of allergic symptoms after exposure to mouse and rat, respectively. Sensitization rates were 28% for mouse epithelium and 23% for rat epithelium. Compared to a positive SPT with wheal ≥ 3 mm, presence of sIgE against rodent allergens showed a higher positive predictive value of 87-91% at a cut-off level of 0.35 KUA/L. Agreement between SPT and sIgE test was determined to be fair to moderate. CONCLUSIONS: Sensitization and allergy to mouse and rat were prevalent among laboratory personnel in Korea. When evaluating cases of potential LAA, the sIgE test can provide added diagnostic value if the skin test is positive. Careful interpretation of two tests is required to accurately diagnose LAA.

Design optimization of a 6.4†mm-diameter electromagnetic 2D scanning micromirror.

We present the design optimization, fabrication, and analysis of an electromagnetic biaxial scanning micromirror with 6.4 mm-diameter. The scanner is composed of a micromirror supported by two concentric gimbal structures with unique single turn coil. A cylindrical permanent magnet assembly is placed under the micromirror to provide a radial magnetic field for actuation. Lumped element model parameters and magnetic circuit have been optimized to maximize the driving torque. Fabricated micromirror has been actuated at 300 Hz and 1,010 Hz and maximum optical scan angle of 25.6° and 35.3° have been obtained for the vertical and horizontal scans, respectively. Crosstalk during the actuation has been analyzed, and improved models have been proposed to reduce the crosstalk.

Cough persistence in adults with chronic cough: A 4-year retrospective cohort study.

BACKGROUND: There is very limited evidence regarding long-term prognosis of chronic cough. We examined longitudinal outcomes among patients with chronic cough, and explored predictors of cough persistence. METHODS: A retrospective cohort was constructed of adults who had newly visited a specialist cough clinic in 2012-2013. All had undergone systematic investigation for chronic cough. The Hull Airway Reflux Questionnaire (HARQ) was administered to assess reflux cough symptoms. A follow-up survey was conducted in 2016-2017 to assess cough persistence. RESULTS: From 418 candidates, 323 participated in the follow-up study; main analyses focused on patients with chronic persistent cough (n = 64; 19.8%) and remitted cough (n = 193; 59.8%). Compared with remitted cough group, chronic persistent cough group had more family history of chronic cough (17.2% vs. 4.7%, p = 0.001) and cold air-sensitive cough (62.5% vs. 44.6%, p = 0.013). The total HARQ score did not differ; however, two items (cough with eating and cough with certain foods) scored significantly higher in chronic persistent cough. In multivariate analyses, a family history of chronic cough (adjusted odds ratio 4.27 [95% confidence interval 1.35-9.89]), cold air-sensitive cough (2.01 [1.09-3.73]), and cough with eating (1.22 [1.02-1.45]) were associated with chronic persistent cough at 4 years. CONCLUSIONS: Cough persists in about 20% of patients after 4 years following systematic assessment and treatments. Several cough characteristics, such as family history, cold air-sensitivity, or reflux cough, may be associated with cough persistence. Larger cohort studies are warranted to further understand long-term prognosis and confirm predictors of persistence in patients with chronic cough.

Chronic cough in the elderly.

Chronic cough is a multi-factorial syndrome commonly presenting as cough hypersensitivity in adult patients. It is a common medical condition in the communities but is more prevalent in older adults. Elderly patients (≥65 years) frequently suffer from multiple comorbidities, which may lead to more clinical heterogeneity in chronic cough and pose diagnostic and therapeutic challenges. Hyposensitivity in cough reflex, probably resulting from central nervous system illnesses, is another potential concern. Despite these complexities and challenges, elderly-specific issues have rarely been addressed in current clinical practice guidelines for chronic cough. Considering recent trends in global population aging, the burden of elderly chronic cough is expected to increase into the near future. This review aimed to respond to following clinical questions: (1) is chronic cough a more heterogeneous condition in the elderly compared to younger adults; and (2) are there additional considerations when choosing the diagnostic and therapeutic approaches to this condition in the elderly?

Impact of Cough and Unmet Needs in Chronic Cough: A Survey of Patients in Korea.

PURPOSE: Chronic cough is a common problem in various populations. The present study assessed the impact of cough and unmet needs in Korean patients with chronic cough. METHODS: This cross-sectional multi-center study enrolled adult patients newly referred to clinic for assessment of chronic cough. A second group of patients with unexplained chronic cough following detailed assessment were recruited for comparison. Patients completed self-reported questionnaires, including cough characteristics, impact of cough on daily life, and unmet needs. RESULTS: A total of 447 subjects were recruited from six referral clinics, including 408 with chronic cough and 39 with unexplained chronic cough. Almost all patients reported that cough impacted their daily lives. Psychosocial impacts were more evident in unexplained cough patients compared to newly referred patients. Approximately 75% of newly referred patients had previously sought medical care for cough on multiple occasions, but the effectiveness of treatment was limited (70.3%) or absent (17.3%). The most frequent unmet need was the ineffectiveness of treatment (49.3%), followed by unclear diagnosis (30.1%). The majority of participants ( > 80%) expressed the need for further information on accessing cough specialists and disease management. The main problem faced by unexplained cough patients was poor cough control despite treatment (64%). CONCLUSIONS: Chronic cough has a substantial impact on daily life and is worst in those whose cough remains unexplained following assessment. Ineffectiveness of treatment and unclear diagnosis were major unmet needs. Medical information about chronic cough was also lacking. Improvements in the management of chronic cough patients in Korea are necessary.

Diagnostic accuracy of fractional exhaled nitric oxide measurement in predicting cough-variant asthma and eosinophilic bronchitis in adults with chronic cough: A systematic review and meta-analysis.

BACKGROUND: Individual studies have suggested the utility of fractional exhaled nitric oxide (Feno) measurement in detecting cough-variant asthma (CVA) and eosinophilic bronchitis (EB) in patients with chronic cough. OBJECTIVE: We sought to obtain summary estimates of diagnostic test accuracy of Feno measurement in predicting CVA, EB, or both in adults with chronic cough. METHODS: Electronic databases were searched for studies published until January 2016, without language restriction. Cross-sectional studies that reported the diagnostic accuracy of Feno measurement for detecting CVA or EB were included. Risk of bias was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy of Feno measurement. RESULTS: A total of 15 studies involving 2187 adults with chronic cough were identified. Feno measurement had a moderate diagnostic accuracy in predicting CVA in patients with chronic cough, showing the summary area under the curve to be 0.87 (95% CI, 0.83-0.89). Specificity was higher and more consistent than sensitivity (0.85 [95% CI, 0.81-0.88] and 0.72 [95% CI, 0.61-0.81], respectively). However, in the nonasthmatic population with chronic cough, the diagnostic accuracy to predict EB was found to be relatively lower (summary area under the curve, 0.81 [95% CI, 0.77-0.84]), and specificity was inconsistent. CONCLUSIONS: The present meta-analyses indicated the diagnostic potential of Feno measurement as a rule-in test for detecting CVA in adult patients with chronic cough. However, Feno measurement may not be useful to predict EB in nonasthmatic subjects with chronic cough. These findings warrant further studies to validate the roles of Feno measurement in clinical practice of patients with chronic cough.

Work-related asthma in adults with severe asthma from the Korean Severe Asthma Registry (KoSAR).

Background: Exposure to allergens or irritants in the workplace may affect asthma control and the quality of life (QoL) of patients with asthma. Objective: To examine the prevalence and characteristics of work-related asthma (WRA) in adult patients with severe asthma. Methods: We analyzed data from the Korean Severe Asthma Registry (KoSAR), which is a nationwide multicenter observational study on severe asthma in Korea. Severe asthma was defined according to the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. WRA was identified on the basis of asthma symptom aggravation at the workplace, as indicated by responses to a structured questionnaire. We compared the demographic and clinical characteristics and QoL between adult patients with severe asthma and WRA and those without WRA. Results: Among 364 patients with severe asthma who were employed at the time of enrollment, 65 (17.9%) had WRA. There were no significant differences in age, sex, obesity, or smoking history between the WRA and non-WRA groups. However, individuals with WRA exhibited a higher prevalence of anxiety (7.7% vs 2.4%, P = 0.046) and depression (12.3% vs 3.7%, P = 0.010) than those without. The levels of asthma control, lung function, and frequency of asthma exacerbations were similar between the two groups, but patients with WRA reported lower QoL, as determined by the Quality of Life Questionnaire for Adult Korean Asthmatics (56.6 ± 14.6 vs. 63.5 ± 13.9, P < 0.001). Conclusion: Patients with severe asthma and WRA are more likely to experience anxiety and depression and have lower QoL than those without WRA.

Real-World Effectiveness of Biologics in Patients With Severe Asthma: Analysis of the KoSAR.

PURPOSE: Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the therapeutic effects of biologics in clinical practice. METHODS: This multicenter, retrospective cohort study included 136 patients who received biologics for at least 4 months between September 2017 and July 2022 at 25 medical centers affiliated with the Korean Severe Asthma Registry (KoSAR). The study evaluated the treatment effects, including acute exacerbation rates, maintenance of oral corticosteroid dosages, lung function, quality of life, blood eosinophil count, and fractional exhaled nitric oxide (FeNO) levels, by comparing measurements before and after 4 months of biologic treatment. Responses for each medication was evaluated based on the Global Evaluation of Treatment Effectiveness score, and any adverse reactions were summarized. RESULTS: With the administration of biologics over the course of 4 months, there was a reduction in asthma acute exacerbations, a significant improvement in lung function, and a significant decrease in daily maintenance dose of oral steroid. Blood eosinophil counts decreased in the mepolizumab and reslizumab groups, while FeNO levels decreased only in the dupilumab group. The Asthma Control Test, Quality of Life Questionnaire for Adult Korean Asthmatics, and the EuroQol-visual analogue scale scores showed a significant improvement. Most patients (80.15%) responded to the biologic treatment. Meanwhile, non-responders often had chronic rhinosinusitis as a comorbidity, exhibited lower lung function, and required higher doses of oral steroids. No severe adverse events were reported. CONCLUSIONS: Biologics are highly effective in Korean patients with Type 2 severe asthma, significantly reducing acute exacerbation rates and doses of oral corticosteroids, while also improving lung function. Therefore, it seems beneficial to administer biologics without any restrictions to patients exhibiting Type 2 severe asthma.

Characteristics of Severe Asthma in the Elderly: Observations From the Korean Severe Asthma Registry (KoSAR).

PURPOSE: Few studies have compared the clinical characteristics of severe asthma (SA) in elderly patients compared to that in nonelderly patients. METHODS: We analyzed data from the Korean SA Registry, a nationwide, real-world observational study of SA in Korea. The baseline clinical characteristics, disease control status, and medication use of the patients were compared between elderly (≥ 65 years) and nonelderly groups. RESULTS: Of the 864 patients with SA, 260 (30.1%) were in the elderly group. The elderly group had lower atopy rate, but had higher prevalence of chronic obstructive pulmonary disease (COPD), hypertension, and osteoporosis than did the nonelderly group. The elderly group had a lower rate of type 2 inflammation and lower levels of forced expiratory volume in 1 second (FEV1) (% predicted) and FEV1/forced vital capacity ratio than did the nonelderly group (P < 0.05 for all). However, asthma symptom scores and the frequency of asthma exacerbation were not significantly different between the 2 groups. Of controller medications, biologics were less frequently used in the elderly group (P < 0.05 for all). CONCLUSIONS: SA in the elderly is characterized by lower lung function, less type 2-low airway inflammation, and comorbidity with COPD. These findings are being taken into consideration in the management of elderly patients with SA in real-world clinical practice.

The KAAACI Guidelines for Sublingual Immunotherapy.

Allergen immunotherapy is regarded as the only disease-modifying treatment option for various allergic conditions, including allergic rhinitis and asthma. Among the routes of administration of allergens, sublingual immunotherapy (SLIT) has gained clinical interest recently, and the prescription of SLIT is increasing among patients with allergies. After 30 years of SLIT use, numerous pieces of evidence supporting its efficacy, safety, and mechanism allows SLIT to be considered as an alternative option to subcutaneous immunotherapy. Based on the progressive development of SLIT, the current guideline from the Korean Academy of Asthma, Allergy, and Clinical Immunology aims to provide an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. This guideline addresses the use of SLIT, including 1) mechanisms of action, 2) appropriate patient selection for SLIT, 3) the currently available SLIT products in Korea, and 4) updated information on its efficacy and safety. This guideline will facilitate a better understanding of practical considerations for SLIT.