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This part reviews the management of chronic cough and proposes a management algorithm. Despite proven improvements in quality of life following chronic cough treatment, a clear understanding of the disease and the evidence for the efficacy of some treatments remain vague. Eight key questions regarding the treatment in the uncertain areas were systematically addressed based on the PICO framework and applying the GRADE system for evidence synthesis to provide the strength of recommendation and quality of evidence for key questions, with narrative components for the description of other chronic cough treatment including non-pharmacological therapy. Practical diagrams were developed to facilitate clinical decision-making on treatment. Our guideline introduces the concept of the cough management process for guiding practitioners to assess chronic cough using a holistic approach.

Chronic cough is a common clinical condition requiring comprehensive assessment. This review employs a symptom-focused approach, prioritizing the presenting symptom of "chronic cough" to mirror real-world clinical practice. Ten key questions regarding the investigations in the uncertain areas were systematically addressed based on the PICO framework and applying the GRADE system for evidence synthesis to provide the strength of recommendation and quality of evidence for key questions. Practical diagrams were developed to facilitate clinical decision-making. The initial evaluation involves screening for red flag signs requiring urgent attention, followed by a detailed history-taking and physical examination. A chest radiograph is recommended as the first-line investigation. The primary objective of the initial evaluation is to identify the cause and initiate appropriate treatment. If history and physical examination prove insufficient for a definitive diagnosis, referral to a specialist is advised for further specific testing. The recommendations on specific testing include fractional exhaled nitric oxide for cough variant asthma, nasal endoscopy or digital endoscopy (optional) for upper airway cough syndrome, paranasal sinus computed tomography (CT) for chronic rhinosinusitis, and laryngoscopy for hoarseness. Spirometry is for the diagnosis of obstructive airway diseases, and peak flow variability or bronchial challenge tests are complements particularly if asthma is suspected. Gastroesophageal reflux (GERD) investigations are for patients with chronic cough without typical GERD symptoms. Sinus radiographs and chest CT are not routinely recommended. Our guideline distinguishes itself by prioritizing a symptom-based clinical evaluation to guide clinicians toward the most probable diagnosis, streamlining the diagnostic process.

Background: Barrier disruption in the airway mucosae has been implicated in allergic type 2 inflammatory diseases such as allergic rhinitis and asthma. Zingiber cassumunar Roxb. has long been used in traditional medicine to treat allergic diseases. The active compound, namely compound D, has proven anti-inflammatory benefits. However, the effect of compound D on allergic inflammation remains unclear., Objective: This study aimed to investigate the protective effects of compound D on allergic inflammation-induced barrier disruption., Methods: Type 2 cytokine (IL-4 and IL-13)-exposed 16HBE human bronchial epithelial cells were treated with compound D. After 24, 48, and 72 h, cytotoxicity, epithelial integrity, and tight junction (TJ) disruption were determined by viability assays, transepithelial electrical resistance measurement, and immunofluorescence staining, respectively. Moreover, the mechanism of action of compound D was investigated by western blotting., Results: Compound D (100 and 200 µM) prevented IL-4/IL-13-induced barrier disruption at 24 and 48 h with no effect on cell viability. Compound D rescued the localization of ZO-1 to pericellular areas, and the barrier-protective effect of compound D was mediated by inhibiting STAT6 signaling., Conclusions: Compound D can suppress IL-4/IL-13-induced epithelial inflammation and TJ disruption through STAT6 inhibition. The agent is a promising candidate for therapeutic or adjunctive treatment of type 2 inflammation-associated diseases, including asthma.

Introduction: Asthma management is strongly dependent on physician and patient beliefs and perceptions about the disease and its long-term treatment. The APPaRENT 3 study was conducted to explore factors influencing treatment choice and to understand patients' and physicians' attitudes and perspectives on the use of controller inhalers in regular versus flexible dosing for asthma management., Methods: This cross-sectional survey of patients with asthma and treating physicians was conducted in seven countries: Indonesia, Malaysia, Philippines, Thailand, Vietnam (patient survey only), Saudi Arabia, and the United Arab Emirates. Assessment was carried out through an online/face-to-face questionnaire, where patients' viewpoints were focused on their attitudes and beliefs about asthma and treatment adherence, whereas physicians' viewpoints were gathered on their attitudes and beliefs about asthma management, knowledge of and adherence to asthma treatment guidelines, and asthma treatment regimens., Results: Overall, 1400 patients (mean age, 34 years) and 599 physicians (mean age, 43 years) were included in the survey. Physicians similarly prioritised symptom control (39%) and exacerbation reduction (40%) in moderate asthma, whereas patients prioritised symptom control (41%) over exacerbation reduction (22%). Although both groups (physicians, 86%; patients, 84%) perceived asthma as well-controlled, poor management was evident based on Asthma Control Test (ACT) scores (mean, 15.7; standard deviation, 4.14; 82% had an ACT score < 20) and high symptom burden (39% reported nighttime awakenings or early mornings ≥ 2 nights/week). Most patients (76%) with moderate asthma were prescribed regular dosing, with the most common treatment being inhaled corticosteroid (ICS)/long-acting β 2 -agonist (LABA) with as-needed inhaled short-acting β 2 -agonist (SABA; 20%). Among patients on maintenance and reliever therapy, 93% of patients received a separate inhaled reliever., Conclusions: Despite high symptom burden, patients overestimated their level of asthma control. Physicians prioritised controlling symptoms and reducing exacerbations as treatment goals for moderate asthma, often prescribing regular dosing with ICS/LABA with as-needed inhaled SABA., (© 2024. The Author(s).)

Background: Zingiber cassumunar Roxb. (Phlai) has been used for the treatment of allergies including allergic rhinitis (AR). Although the anti-histamine effects have been reported, assessment of nasal cytokine and eosinophil production had not been investigated., Objective: This study aimed to examine the effect of Phlai on alterations in nasal pro-inflammatory cytokine levels and eosinophil counts in nasal mucosa., Methods: This was a randomized, double-blind, three-way crossover study. Nasal concentrations of cytokines, namely interleukin (IL)-4, IL-5, IL-13 and interferron-gamma (IFN-γ), nasal smear eosinophilia as well as total nasal symptom score (TNSS) were evaluated before and after a 4 weeks treatment with 200 mg Phlai capsules or placebo in 30 AR patients., Results: We observed significant (p < 0.05) reduction in IL-5, IL-13 as well as the number of eosinophils in subjects given Phlai. The degree of improvement of TNSS after Phlai treatment was initially manifested in week 2 with the greatest effect in week 4. In contrast, there were no significant differences in all nasal cytokines, eosinophil counts or TNSS between before and after receiving placebo., Conclusions: These findings provided the first evidence for the anti-allergic effect of Phlai which possibly involved inhibition of nasal pro-inflammatory cytokines production and eosinophilic recruitment. Phlai thus represents a promising herbal medicine for alleviating inflammation and AR symptoms.

Background: Asthma and allergic rhinitis (AR) can coexist and cause disabilities. This study aimed to assess the association between AR, asthma control, asthma-related quality of life, and other comorbidities., Methods: A cross-sectional study was conducted in adults with asthma in six hospitals in Thailand. The outcomes were association of asthma control assessed by the asthma control test (ACT), AR, and asthma comorbidities. Not-well-controlled asthma was defined as ACT scores ≤22. The severity of AR was determined by visual analog scale (VAS). Severe AR was defined as VAS ≥5. Asthma-related quality of life (AQLQ), comorbidities, and total IgE were recorded., Results: A total of 682 asthmatic patients were included. Median (IQR) age was 58.0 (47.0-64.0) years. 69.9% were female. Not-well-controlled asthma was present in 44.7%. The prevalence of AR was 86.1%. Moderate/severe persistent AR was diagnosed in 21.7% and severe AR was diagnosed in 30.2% of the patients. Inhaled corticosteroid-containing regimens were prescribed in 97.7% of patients. Intranasal corticosteroid and antihistamine were prescribed in 65.7 and 31.7%, respectively. Patients with not-well-controlled asthma had higher body mass index, VAS scores, proportions of pollution exposure, aeroallergen sensitization, severe AR, nasal polyp, urticaria, food allergy, gastroesophageal reflux disease, depression and anxiety, peptic ulcer, and asthma exacerbations, but younger age, lower AQLQ scores, and lower FEV 1 . Correlation was found between AR severity and ACT ( r  = -0.461, p  < 0.001), AQLQ ( r  = -0.512, p  < 0.001), and total IgE ( r  = 0.246, p  < 0.023). Multiple regression analysis revealed that ACT, AQLQ, and percentage of FEV 1 /FVC were significantly associated with severe AR., Conclusion: Allergic rhinitis is prevalent in Thai asthmatic patients. AR severity is associated with asthma control, quality of life, and pulmonary function. Comprehensive care is essential for patients with uncontrolled asthma, particularly when coexisting with conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sriprasart, Saiphoklang, Kawamatawong, Boonsawat, Mitthamsiri, Chirakalwasan, Chiewchalermsri, Athipongarporn, Kamalaporn, Kornthatchapong, Kulpraneet, Sompornrattanaphan, Oer-Areemitr, Rerkpattanapipat, Silairatana, Thawanaphong, Gaensan, Jirakran and Poachanukoon.)

Background: Despite nebulized budesonide being identified by the Global Initiative for Asthma report as a viable alternative to inhaled corticosteroids (ICS) delivered by pressurized metered-dose inhalers (pMDIs) with spacers, practical guidance on nebulized corticosteroid use in the pediatric population remains scarce., Objective: To review the current literature and provide practical recommendations for nebulized budesonide use in children aged ≤ 5 years with a diagnosis of asthma., Methods: A group of 15 expert pediatricians in the respiratory and allergy fields in Thailand developed Delphi consensus recommendations on nebulized budesonide use based on their clinical expertise and a review of the published literature. Studies that evaluated the efficacy (effectiveness) and/or safety of nebulized budesonide in children aged ≤ 5 years with asthma were assessed. AR patients., Results: Overall, 24 clinical studies published between 1993 and 2020 met the inclusion criteria for review. Overall, results demonstrated that nebulized budesonide significantly improved symptom control and reduced exacerbations, asthma-related hospitalizations, and the requirement for oral corticosteroids compared with placebo or active controls. Nebulized budesonide was well tolerated, with no severe or drug-related adverse events reported. Following a review of the published evidence and group consensus, a treatment algorithm as per the Thai Pediatric Asthma 2020 Guidelines was proposed, based on the availability of medications in Thailand, to include nebulized budesonide as the initial treatment option alongside ICS delivered by pMDIs with spacers in children aged ≤ 5 years., Conclusions: ThNebulized budesonide is an effective and well-tolerated treatment option in children aged ≤ 5 years with asthma.

Background: Preclinical studies demonstrated anti-inflammatory effects of Zingiber montanum (J.König) Link ex Dietr.(Phlai). However, its clinical effect on allergic rhinitis (AR) is not evident., Objective: We sought to assess the efficacy and safety of Phlai for treating AR., Methods: A phase 3, randomized, double-blind, placebo-controlled study was conducted. Patients with AR were randomized into three groups and received Phlai 100 mg or Phlai 200 mg or placebo once a day for four weeks. The primary outcome was a change in the reflective total five symptom score (rT5SS). The secondary outcomes were the change in the instantaneous total five symptom score (iT5SS), the reflective individual symptom scores (rhinorrhea, nasal congestion, sneezing, itchy nose, itchy eyes), Rhinoconjunctivitis Quality of Life-36 Questionnaire (RCQ-36) score, peak nasal inspiratory flow (PNIF), and adverse events., Results: Two hundred and sixty-two patients were enrolled. Compared with placebo, Phlai 100 mg improved rT5SS [adjusted mean difference (aMD) -0.62; 95%CI -1.22, -0.03; p = 0.039], rhinorrhea (aMD -0.19; 95%CI -0.37, 0.002; p = 0.048), itchy nose (aMD -0.24; 95%CI -0.43, -0.05; p = 0.011), and itchy eyes (aMD -0.19; 95%CI -0.36, -0.02; p = 0.033) at week 4. Nasal obstruction, sneezing, iT5SS, overall RCQ-36 score, PNIF did not reach statistical significance. Phlai 200 mg did not bring additional benefits compared to 100 mg. Adverse events were similar among groups., Conclusions: Phlai was safe. At four weeks, there were small improvements in rT5SS, together with the individual symptoms of rhinorrhea, itchy nose, and itchy eyes.

Background: The accuracy of an atopy patch test (APT) for fresh cow's milk allergy is controversial. Few studies have focused on commercial extract solutions. We aimed to evaluate the diagnostic performance of the APT in cow's milk allergic children using fresh cow's milk and commercial extracts of cow's milk and its components including casein, α-lactalbumin, and β-lactoglobulin., Methods: A prospective study was carried out in children with a history of cow's milk allergy. Children underwent the skin prick test (SPT) and APT with fresh cow's milk, powdered cow's milk, and commercial extracts of cow's milk, casein, α-lactalbumin, and β-lactoglobulin. Oral food challenge (OFC) was confirmed in all children., Results: A total of 37 patients participated (mean age 13.14 ± 7.26 months). Only 5 (13.51%) patients had positive OFC to cow's milk. The sensitivity of the APT using fresh cow's milk was 40%, specificity was 65.6%, PPV was 15.4%, and NPV was 87.5%. The sensitivity of the APT using powdered cow's milk was 40%, 60.7% for specificity, 15.4% for PPV, and 58% for NPV. The sensitivity and PPV of the APT using commercial solutions of cow's milk, casein, α-lactalbumin, and β-lactoglobulin were zero. The specificities were 90.6%, 93.8%, 100%, and 100% for α-lactalbumin, cow's milk, casein, and β-lactoglobulin, respectively., Conclusions: APT using commercial solutions showed higher specificity than fresh milk. The specificity increased using a protein component allergen., (© 2023. The Author(s).)

Objective: In order to understand the role of regular controller inhaled corticosteroids (ICS) versus as-needed ICS-formoterol in managing mild asthma, we performed a modified Delphi procedure., Methods: Opinions from 16 respiratory experts to three surveys and during a virtual scientific workshop helped to develop final consensus statements (pre-defined as 70% agreement)., Results: Thirteen participants completed all rounds (response rate 81%). At the end of the procedure, there was final consensus on: regular daily ICS being the recommended treatment approach in mild persistent asthma, with better symptom control and robust long-term clinical data compared with as-needed ICS-formoterol (85%); to avoid noncompliance, frequently seen in mild asthma patients, regular ICS dosing should be accompanied by ongoing education on treatment adherence (100%); treatment aims should be targeting asthma control (92%) and reduction of exacerbation risk (85%). No consensus was reached on whether GINA or national guidelines most influence prescribing decisions., Conclusions: It is important to encourage patients to be adherent and to target both asthma control and exacerbation risk reduction. There is robust clinical evidence to support proactive regular dosing with ICS controller therapy plus as-needed short-acting beta-agonists for the management of patients with mild asthma.

Background: Patterns of aeroallergen sensitization vary by countries. Testing with the minimum number of allergens is important to identify sensitized patients for a cost-effective approach. We aimed to assess the minimal skin prick test (SPT) panel to identify sensitized children with allergic respiratory diseases., Methods: The SPT results from January 2020 to December 2021 in children aged 2-18 years with symptoms of asthma or allergic rhinitis or both were retrospectively reviewed. All children received 11 allergen extracts (Dermatophagoides pteronyssinus [Der p], Dermatophagoides farinae [Der f], American cockroach, German cockroach, cat, dog, Bermuda grass, careless weed, Timothy, Acacia, and molds). The conditional approach was used to determine the allergen selection for the SPT panel., Results: A total of 688 children were enrolled (mean age = 8.14 ± 3.91 years). The sensitization results were Der p (57.85%), Der f (55.09%), German cockroach (18.02%), American cockroach (17.01%), cat (11.77%), Acacia (3.49%), Bermuda grass (3.34%), molds (3.05%), Timothy (2.33%), dog (1.89%), and careless weed (1.60%). Der p, Der f, and German cockroach were required to detect at least 95% of sensitized children. If the SPT panel added Acacia, cat, American cockroach, Bermuda grass, and careless weed, sensitization was detected in 99-100% of cases., Conclusions: Indoor allergens (Der p, cockroach, and cat) were common causes of sensitization in Thai children with allergic respiratory diseases. Eight allergens were sufficient for sensitization identification in Thai children with asthma or allergic rhinitis or both in clinical practice., (© 2022. The Author(s).)

Background: Nasal irrigation is an effective component of sino-nasal disease management. Nonetheless, bacterial contamination is worrisome., Objective: To study bacterial colonization incidence using squeeze-bottle nasal irrigation devices, after disinfection with soap or soap-plus-microwave technique, in pediatric acute rhinosinusitis., Methods: A randomized, prospective, controlled study was conducted on acute rhinosinusitis children, aged 2-15 years. Each participant was randomized into a soap-cleaning or soap-plus- microwave group. For a two-week period, participants irrigated their nostrils with NSS twice daily and cleaned the bottle after each use. In the end, bottles were sent to a microbiological laboratory for bacterial identification., Results: The mean 5S Score and satisfaction score gradually improved in both groups with no significant differences between groups. Bacterial identification frequency in the soap group was slightly higher than in the soap-plus-microwave one, without statistical significance. For safety and tolerability, all participants reported 100% adherence to nasal irrigation. The soap-plus-microwave group reported more minor adverse outcomes than the soap-cleaning one. No thermal deformation of irrigation bottles was observed., Conclusions: Regular cleaning of nasal irrigation devices is needed to minimize bacterial contamination. Only soap or soap plus microwave disinfection appeared simple and safe for disinfection. Both techniques can equally minimize the rate of bacterial contamination. Although no gross thermal deformation at optimal power and duration, chemical irritants after high power or long microwave durations may be a concern.

The multidisciplinary experts in Thailand developed an asthma management recommendation that was relevant to low-middle income countries (LMICS). Populations level consideration about asthma management is emphasized. The healthcare systems, access to and availability of treatments as well as the asthma populations vary from country to country in LMICS. The feasibility in clinical practice for implementation is also a major issue. For these reasons, the practice guidelines that are relevant to local contexts are essential to improve better asthma control. Furthermore, integrative and collaboration between asthma experts and the public health sector to implement and discriminate such guidelines will help to achieve these challenging goals. The topics covered include the current asthma situation in Thailand and the Asia-Pacific region, the definition of asthma, asthma diagnosis, assessment of asthma patients, asthma treatment - both pharmacological and non-pharmacological, management of asthma exacerbation, management of asthma comorbidities, treatment of asthma in special conditions, severe and uncontrolled asthma, Thai alternative medicine and asthma, and asthma and coronavirus disease-19 (COVID-19).

Objective: The aim of this study was to determine if there is an association between the salivary protein profile and disease control in asthma., Methods: Thirty asthmatic patients (17 adults and 13 children) participated in this study. Saliva samples were collected from healthy subjects, controlled and uncontrolled asthmatics. Individual samples from each group were combined to form a pooled sample, from which proteomic analysis was performed using gel-based quantitative proteomics., Results: Fourteen out of thirty asthmatics were classified to be controlled asthma. Most of asthmatics received inhaled corticosteroids as the controller medications. SDS-PAGE showed predominant bands at high molecular weight in asthmatic saliva compared to that of the controls. Shotgun proteomic analyses indicated that 193 salivary proteins were expressed in both controlled and uncontrolled asthmatics. They were predicted to associate with proteins involved in pathogenesis of asthma including IL-5, IL-6, MCP-1, VEGF, and periostin and asthma medicines (Cromolyn, Nedocromil, and Theophylline). Nucleoside diphosphate kinase (NME1-NME2) only expressed in controlled asthmatics whereas polycystic kidney and hepatic disease 1 (PKHD1)/fibrocystin, zinc finger protein 263 (ZNF263), uncharacterized LOC101060047 (ENSG00000268865), desmoglein 2 (DSG2) and S100 calcium binding protein A2 (S100A2) were only found in uncontrolled asthma. Therefore, the six proteins were associated with disease control in children and adults with asthma., Conclusion: Our findings suggest that NME1-NME2, PKHD1, ZNF 263, uncharacterized LOC101060047, DSG 2 and S100 A2 in saliva are associated with disease control in asthma.