Expert panel consensus recommendations on the utilization of nebulized budesonide for managing asthma and COPD in both stable and exacerbation stages in Thailand.

OBJECTIVE: This study investigated the utilization of nebulized budesonide for acute asthma and COPD exacerbations as well as for maintenance therapy in adults. DATA SOURCES: We conducted a search on PubMed for nebulized budesonide treatment. SELECTED STUDIES: Selecting all English-language papers that utilize Mesh phrases "asthma," "COPD," "budesonide," "nebulized," "adult," "exacerbation," and "maintenance" without temporal restrictions, and narrowing down to clinical research such as RCTs, observational studies, and real-world studies. RESULTS: Analysis of 25 studies was conducted to assess the effectiveness of nebulized budesonide in asthma (n = 10) and COPD (n = 15). The panel in Thailand recommended incorporating nebulized budesonide as an additional or alternative treatment option to the standard of care and systemic corticosteroids (SCS) based on the findings. CONCLUSION: Nebulized budesonide is effective and well-tolerated in treating asthma and COPD, with less systemic adverse effects compared to systemic corticosteroids. High-dose nebulized budesonide can enhance clinical outcomes for severe and mild exacerbations with slow systemic corticosteroid response. Nebulized budesonide can substitute systemic corticosteroids in some situations.

Allergic rhinitis and other comorbidities associated with asthma control in Thailand.

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 FEV1. 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 FEV1/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.

Critically ill patients with edema and ascites may experience subtherapeutic anti-factor Xa levels following abdominal subcutaneous enoxaparin treatment.

Enoxaparin is a low molecular weight heparin that is principally prescribed for the treatment and prevention of thromboembolic disorders. In clinical practice, the abdominal site for subcutaneous enoxaparin administration is most preferable because of its simplicity and safety. However, subcutaneous enoxaparin bioavailability in critically ill patients with ascites is uncertain. According to this case report, the bioavailability and absorption of subcutaneous enoxaparin was potentially impaired in a critically ill patient with ascites and local edema based on the therapeutic drug monitoring of anti-factor Xa levels.

A Prospective Study of Plasma and Bronchoalveolar Lavage Fluid CMV DNA Load Quantification for the Diagnosis and Outcome of CMV Pneumonitis in Immunocompromised Hosts.

BACKGROUND: Molecular testing has been utilized for cytomegalovirus (CMV) pneumonitis (CMVP) diagnosis, although its validity and optimal cut-off values remain limited. METHODS: A prospective study of CMVP diagnosis among immunocompromised patients was conducted by measuring quantitative CMV DNA polymerase chain reaction in plasma and bronchoalveolar lavage fluid (BALF). RESULTS: Forty-five adult immunocompromised patients were investigated. Thirty-two patients (71%) received immunosuppressive therapy. Eleven patients (24%) were confirmed to have CMVP. Of those, three and eight patients were classified as proven and probable CMVP, respectively. Median (IQR) plasma CMV DNA loads in CMVP and non-CMVP were 41,939 (4,424-122,608) and 0 (0-44) IU/mL, respectively (p<0.001). Median (IQR) BALF CMV DNA loads in CMVP and non-CMVP were 379,652 (163,800-1,254,000) and 0 (0-1,348) IU/mL, respectively (p<0.001). A significant correlation was observed between plasma and BALF CMV DNA loads (r=0.887, p<0.001). Plasma CMV DNA load of 831 IU/mL was established as a cut-off value for diagnosing CMVP (AUC 0.9987, sensitivity 100%, specificity 94.1%, positive predictive value 84.5%, negative predictive value 100%). CONCLUSIONS: A strongly positive correlation was observed between CMV DNA loads measured in plasma and BALF. CMV DNA load quantification could potentially assist in diagnosing CMVP in immunocompromised patients, although bronchoscopy remains encouraged for a definitive diagnosis.

Guidelines for the management of asthma in adults: Evidence and recommendations.

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).

Phosphodiesterase-4 Inhibitors for Non-COPD Respiratory Diseases.

Selective phosphodiesterase (PDE) inhibitors are a class of nonsteroid anti-inflammatory drugs for treating chronic inflammatory diseases. Modulation of systemic and airway inflammation is their pivotal mechanism of action. Furthermore, PDE inhibitors modulate cough reflex and inhibit airway mucus secretion. Roflumilast, a selective PDE4 inhibitor, has been extensively studied for the efficacy and safety in chronic obstructive pulmonary disease (COPD) patients. According to the mechanisms of action, the potential roles of PDE inhibitors in treating chronic respiratory diseases including severe asthma, asthma-COPD overlap (ACO), noncystic fibrosis bronchiectasis, and chronic cough are discussed. Since roflumilast inhibits airway eosinophilia and neutrophilia in COPD patients, it reduces COPD exacerbations in the presence of chronic bronchitis in addition to baseline therapies. The clinical studies in asthma patients have shown the comparable efficacy of roflumilast to inhaled corticosteroids for improving lung function. However, the clinical trials of roflumilast in severe asthma have been limited. Although ACO is common and is also associated with poor outcomes, there is no clinical trial regarding its efficacy in patients with ACO despite a promising role in reducing COPD exacerbation. Since mucus hypersecretion is a result of neutrophil secretagogue in patients with chronic bronchitis, experimental studies have shown that PDE4s are regulators of the cystic fibrosis transmembrane conductance regulator (CFTR) in human airway epithelial cells. Besides, goblet cell hyperplasia is associated with an increased expression of PDE. Bronchiectasis and chronic bronchitis are considered neutrophilic airway diseases presenting with mucus hypersecretion. They commonly coexist and thus lead to severe disease. The role of roflumilast in noncystic fibrosis bronchiectasis is under investigation in clinical trials. Lastly, PDE inhibitors have been shown modulating cough from bronchodilation, suppressing transient receptors potential (TRP), and anti-inflammatory properties. Hence, there is the potential role of the drug in the management of unexplained cough. However, clinical trials for examining its antitussive efficacy are pivotal. In conclusion, selective PDE4 inhibitors may be potential treatment options for chronic respiratory diseases apart from COPD due to their promising mechanisms of action.

Efficacy and safety of inhaled nebulized sodium nitrite in asthmatic patients.

BACKGROUND: Nitrite is a physiologic nitric oxide (NO) derivative that can be bioactivated to NO. NO has been shown to attenuate airway inflammation and enhance the anti-inflammatory effect of corticosteroids in the animal model of asthma. Here, we aimed to investigate the efficacy and safety of inhaled sodium nitrite as add-on therapy with inhaled corticosteroid (ICS) in adult patients with persistent asthma. METHODS: In protocol 1, 10 asthmatic patients were administered a single dose of nebulized 15-mg sodium nitrite to assess safety, effect on lung function, and pharmacokinetics of nitrite within 120 min. In protocol 2, 20 patients were randomly assigned to a nitrite (15 mg twice daily) group or a placebo group to assess the efficacy over 12 weeks. The primary outcome was the forced expiratory volume in 1 s (FEV1). The secondary outcomes were other lung function parameters, unplanned asthma-related visits at the emergency department (ED) or outpatient department (OPD), admission days, asthma control test (ACT), and safety. RESULTS: Nebulized sodium nitrite had neither acute adverse effect nor effect on lung function test within 120 min. No blood pressure change was seen. At week 12, FEV1 increased in the nitrite group, whereas there was no change in the placebo group. There were 5 events of asthma exacerbation, 4 ED visits, and one unplanned OPD visit in the placebo group, but none of these was noted in the nitrite group. There was no change in ACT scores in both groups. No adverse event was reported during 12 weeks in the nitrite group. There was no change in methemoglobin levels and sputum inflammatory markers. CONCLUSION: From our pilot trial, nebulized sodium nitrite is safe in asthmatic patients, and shows the potential to reduce asthma exacerbation compared with placebo.

Effects of Oral Procaterol for Postinfectious Cough in Adults: Single-Centre, Randomized Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Persistent cough following an upper respiratory tract infection (URTI) is common in clinical practice. We investigated the effects of procaterol on cough-specific quality of life (QoL) and peripheral-airway function among adults suffering from postinfectious cough (PIC). METHODS: This was a prospective, randomized, double-blinded placebo-controlled trial (NCT02349919) conducted at a university hospital. Seventy-four non-asthmatic adults who had persistent post-URTI cough for ≥3 weeks were assessed by a physical examination, chest/paranasal sinus radiographs, spirometry, and impulse oscillometry (IOS) and were allocated to receive procaterol or placebo for 4 weeks. The Thai version of the Leicester Cough Questionnaire (LCQ-T), spirometry and IOS were assessed at baseline, 2 weeks, and 4 weeks. RESULTS: Mean LCQ-T total scores for the procaterol group (10.8) and placebo group (10.9) at baseline were not significantly different (P=0.821). After adjustment for baseline Borg Cough Scale score and post-nasal drip, the mean between-group difference was not significant for LCQ-T total score (-1.26; 95% confidence interval [CI], -2.69 to 0.17), physical domain score (-0.35; 95% CI, -0.76 to 0.06), psychological domain score (-0.53; 95% CI, -1.06 to 0.01), or social domain score (-0.38; 95% CI, -0.92 to 0.16). Large improvements in LCQ-T total score were reported in both groups after 2 weeks (procaterol, 4.21±2.73; placebo, 5.34±3.2), and 4 weeks (procaterol, 5.94±3.68; placebo, 7.07±3.44). No differences between groups were found in the mean changes of spirometry or IOS parameters after 4 weeks. CONCLUSION: Our study shows that procaterol is not effective in the treatment of PIC, in terms of improvement of cough-specific QoL or peripheral-airway function.

Direct Inhibitory Effect of the PDE4 Inhibitor Roflumilast on Neutrophil Migration in Chronic Obstructive Pulmonary Disease.

Neutrophilic inflammation is characteristic of chronic obstructive pulmonary disease (COPD); yet, there are no effective antiinflammatory therapies. The PDE4 inhibitor roflumilast is approved for use in COPD and suppresses sputum neutrophilia. The mechanism underlying this observation is unclear; therefore, this study addressed whether roflumilast directly affected neutrophil migration. Blood-derived neutrophils were isolated from nonsmokers, smokers, and patients with COPD, and chemotaxis was measured using Boyden chambers. Intracellular calcium ion concentration was measured by fluorimetry, and shape change and CD11b expression were measured by flow cytometry. Neutrophils from patients with COPD showed enhanced chemotactic responses toward both CXCL1 and leukotriene B4 compared with control cells. Chemotaxis was inhibited by both the active metabolite roflumilast N-oxide and rolipram in a concentration-dependent manner with no difference in responsiveness between subjects. Roflumilast N-oxide and rolipram were less efficacious against CXCL1 and leukotriene B4-mediated intracellular calcium ion concentration, suggesting that inhibition was not via this pathway. Both PDE4 inhibitors attenuated chemoattractant-mediated shape change and CD11b upregulation, suggesting common mechanisms. The stable cAMP analog 8-bromoadenosine 3',5'-cAMP inhibited chemotaxis, as did the direct Epac1 (exchange protein directly activated by cAMP 1) activator 8-(4-chlorophenylthio)-2'-O-methyladenosine 3',5'-cAMP but not the direct protein kinase A activator N6-benzoyladenosine-3',5'-cAMP. These data suggest that roflumilast inhibits neutrophil chemotaxis directly via a cAMP-mediated mechanism requiring activation of Epac1 and that Epac1 activators could reduce COPD neutrophilic inflammation.

Assessment of proximal and peripheral airway dysfunction by computed tomography and respiratory impedance in asthma and COPD patients with fixed airflow obstruction.

OBJECTIVE: To ascertain: (i) if elderly patients with fixed airflow obstruction (FAO) due to asthma and chronic obstructive pulmonary disease (COPD) have distinct airway morphologic and physiologic changes; (ii) the correlation between the morphology of proximal/peripheral airways and respiratory impedance. METHODS: Twenty-five asthma cases with FAO and 22 COPD patients were enrolled. High-resolution computed tomography was used to measure the wall area (WA) and lumen area (LA) of the proximal airway at the apical segmental bronchus of the right upper lobe (RB1) adjusted by body surface area (BSA) and bronchial wall thickening (BWT r ) of the peripheral airways and extent of expiratory air trapping (AT exp ). Respiratory impedance included resistance at 5 Hz (R5) and 20 Hz (R20) and resonant frequency (Fres). Total lung capacity (TLC) and residual volume (RV) were measured. RESULTS: Asthma patients had smaller RB1-LA/BSA than COPD patients (10.5 ± 3.4 vs. 13.3 ± 5.0 mm2/m2, P = 0.037). R5(5.5 ± 2.0 vs. 3.4 ± 1.0 cmH2O/L/s, P = 0.02) and R20(4.2 ± 1.7 vs. 2.6 ± 0.7 cmH2O/L/s, P = 0.001) were higher in asthma cases. AT exp and BWT r were similar in both groups. Regression analysis in asthma showed that forced expiratory volume in one second (FEV1) and Fres were associated with RB1-WA/BSA (R2= 0.34, P = 0.005) and BWT r (0.5, 0.012), whereas RV/TLC was associated with AT exp (0.38, 0.001). CONCLUSIONS: Asthma patients with FAO had a smaller LA and higher resistance of the proximal airways than COPD patients. FEV1 and respiratory impedance correlated with airway morphology.

Erratum: Correction of Figure 1: The asthma and chronic obstructive pulmonary disease overlap syndrome in tertiary care setting Thailand.

[This corrects the article on p. 227 in vol. 7, PMID: 29094021.].

Relationship between the presence of bronchiectasis and acute exacerbation in Thai COPD patients.

Background: The prevalence rate of bronchiectasis in COPD is variable. Coexisting bronchiectasis and COPD may influence COPD severity and exacerbation. Objective: We investigated whether bronchiectasis is associated with frequent or severe COPD exacerbation. Lower airway bacterial and mycobacterial infections are a possible mechanism for bronchiectasis. Materials and methods: A cross-sectional study was conducted in 2013-2014. COPD exacerbations and hospitalizations were reviewed. Spirometry and CT were performed. COPD symptoms were assessed by using the COPD assessment test (CAT) and modified Medical Research Council (mMRC) dyspnea scale. Sputum inductions were performed and specimens were sent for microbiology. Results: We recruited 72 patients. Global Initiative for Chronic Obstructive Lung Disease (GOLD) A, B, C, and D, were noted in 20%, 27.1%, 14.3%, and 38.6% of the patients, respectively. Frequent exacerbations (≥2) and/or ≥1 hospitalization in the previous year were observed in 40.3% of patients. Median mMRC of COPD with frequent and non-frequent exacerbations was 1.0 (range 1-2) and 2.0 (range 1-3), (p=0.002), respectively. Median CAT of COPD with frequent and non-frequent exacerbations was 20.5 (3-37) and 11.0 (2-32), (p=0.004), respectively. CT-detected bronchiectasis was observed in 47.2% of patients. Median mMRC of COPD with and without bronchiectasis was 1.0 (0-4) and 1.0 (0-4) (p=0.22), respectively. Median CAT of COPD with and without bronchiectasis was 16.2 (95% CI: 12.9-19.6) and 13.0 (3-37), (p=0.49), respectively. The lower post-bronchodilator forced expiratory volume in 1 second (FEV1) of COPD with frequent exacerbations than those without was noted (p=0.007). The post-bronchodilator forced expiratory volume at 1 second percent in patients with and without bronchiectasis was not different (p=0.91). After adjusting for gender, severity of airflow obstruction, severity of COPD symptoms, the odds ratio for bronchiectasis with frequent and/or severe exacerbation was 4.99 (95% CI: 1.31-18.94), (p=0.018). Neither bacterial nor mycobacterial airway infection was associated with bronchiectasis or frequent exacerbation. Conclusions: Bronchiectasis is common in Thai COPD. It was associated with frequent exacerbation or hospitalization. Mycobacterial tuberculosis in COPD patients with bronchiectasis was uncommon.

Long-term effectiveness of omalizumab treatment in Thai severe asthmatic patients: A real-life experience.

BACKGROUND: To evaluate long-term effectiveness of omalizumab in 'real-life' setting of Thai asthmatic patients. METHODS: We conducted multi-center, observational study in severe asthma patients who received omalizumab in Thailand. Outcomes were asthma exacerbation (hospitalization and ER visit), asthma control test (ACT), and daily ICS dose. Data were evaluated at baseline, 16 Week, and 52 Week. RESULTS: A total of 78 patients received omalizumab treatment (average duration 16.9 months with range 16 weeks-2 years). The mean annualized rate of exacerbations was reduced from baseline (3.79) at Week 16 (3.54) and Week 52 (1.16), (p<0.05), respectively. The mean hospitalization rate was reduced from 0.49 in previous year to 0.15 at Week 16 and 0.19 at Week 52. A reduction in ER visit rates was observed at Week 16 (0.15) and Week 52 (0.97) respectively from baseline (1.44) (p<0.05). The ACT score increased from 15.4 at baseline to 20.6 at Week 16 (p<0.001) and increased to 21.5 at Week 52 (p<0.001). The number of patients with controlled asthma (ACT≥20) increased from 16 of 51 at baseline to 32 of 45 at Week 16 and 25 of 32 at week 52, respectively. The median daily dose of ICS equivalent to fluticasone was reduced from baseline 680 mcg to 500 mcg at Week 52. In all, 22 patients discontinued omalizumab after 1 year. Six patients who discontinued omalizumab were restarted due to relapse of symptoms. CONCLUSIONS: These data confirms the effectiveness of one-year duration of omalizumab treatment in Thai severe asthmatic patients. Furthermore, 27% of patients who discontinued treatment required restarting due to relapse of symptoms.

The asthma and chronic obstructive pulmonary disease overlap syndrome in tertiary care setting Thailand.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is an increasingly recognized clinical entity. ACOS significantly impacts on patient outcome compared to isolated asthma or COPD. However, ACOS definition and diagnosis criteria have not been well standardized. ACOS prevalence and clinical features in Thailand has never been studied. Objective: To investigate the prevalence and clinical features of ACOS compared to isolated asthma or COPD among patients with clinician-diagnosis of obstructive airway diseases. OBJECTIVE: To investigate the prevalence and clinical features of ACOS compared to isolated asthma or COPD among patients with clinician-diagnosis of obstructive airway diseases. METHODS: Spirometry, skin prick test (SPT) and allergens specific IgE (sIgE) were done. Serum total IgE, exhaled nitric oxide (FeNO) and blood eosinophils were measured. High resolution computed tomography (HRCT) was performed. Smoking history, pollution, biomass exposure and symptoms (Asthma Control Test [ACT], COPD assessment test [CAT], Modified Medical Research Council Dyspnea Scale [MMCR]) were assessed. Patients were classified to isolated asthma, COPD or ACOS according to predefined definitions for this study. RESULTS: A total 92 patients were enrolled: 58 patients with clinician-diagnosed of late onset asthma and 34 with clinician-diagnosed COPD. The mean age was 67.4 years. Thirty-four asthma patients (58.6%) were considered to have ACOS with postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio <0.7 and/or presence of emphysema on HRCT. In addition, 10 COPD patients (28.6%) were classified as ACOS if they had bronchodilator reversibility (FEV1 ≥ 12% and ≥ 200 mL) and positive SPT or sIgE. Hence, total of 44 from 92 patients (47.8%) with obstructive airway diseases were found to have ACOS, while isolated asthma and COPD were found in 24 patients equally. No difference in symptoms assessed by CAT, ACT, or MMRC was found between 3 groups of patients. Neither serum total IgE nor blood eosinophils counts distinguished ACOS from asthma and COPD (p = 0.83 and p = 0.40). FeNO was higher in pure COPD than ACOS and asthma (p = 0.03). CONCLUSION: ACOS is prevalent in late-onset asthma or clinician-diagnosed COPD who were treated in tertiary care clinic. However, we found no difference in symptoms, blood eosinophils or serum total IgE between groups.

Minimal Clinically Important Differences (MCIDs) of the Thai Version of the Leicester Cough Questionnaire for Subacute and Chronic Cough.

OBJECTIVES: To investigate the minimal clinically important differences (MCIDs) of the Thai version of the Leicester Cough Questionnaire (LCQ-T) in patients with subacute and chronic cough. METHODS: Patients with cough for 3 or more weeks were recruited from outpatient clinics. They self-completed the LCQ-T at an initial evaluation and repeated the LCQ-T with a Global Rating of Change scale at follow-up. For the anchor-based method, the MCID was defined as a change in the LCQ scores that corresponded to the smallest improvement in Global Rating of Change score (+2 to +3). For distribution-based methods, the MCIDs were estimated from the standard error of measurement and a half and one-third of the SD of the LCQ score changes from baseline to follow-up. RESULTS: A total of 107 patients were included. The causes of cough were postinfectious cough/bronchitis (35.5%), asthma (20.6%), rhinosinusitis (16.8%), bronchiectasis (17.8%), and chronic obstructive pulmonary disease (9.3%). The anchor-based method yielded MCIDs of 1.1, 0.4, 0.4, and 0.4 for the total, physical, psychological, and social domains, respectively. The distribution-based method using standard error qof measurement yielded MCIDs of 0.8, 0.3, 0.3, and 0.3, whereas those using a half SD yielded MCIDs of 2.0, 0.6, 0.8, and 0.8 and those using one-third SD yielded MCIDs of 1.4, 0.4, 0.5, and 0.5 for the total, physical, psychological, and social domains, respectively. CONCLUSIONS: The MCIDs of the LCQ-T for subacute and chronic cough are 1.1, 0.4, 0.4, and 0.4 for the total, physical, psychological, and social domains, respectively. These estimates should be useful in making meaningful interpretations of the changes in quality of life because of cough.

Serum inflammatory biomarkers and clinical outcomes of COPD exacerbation caused by different pathogens.

BACKGROUND AND OBJECTIVE: COPD exacerbation is characterized by worsening of symptoms, warranting change in treatment. Systemic and airway inflammation play roles in the pathogenesis of COPD exacerbation. We hypothesized whether increased serum inflammatory biomarkers are associated with the clinical outcomes of COPD exacerbation caused by different infectious pathogens. METHODS: COPD patients with exacerbation were recruited from a hospital emergency department during 2014-2015. Serum procalcitonin (PCT) and C-reactive protein (CRP) were measured. Dyspnea, eosinopenia, consolidation, acidemia, and atrial fibrillation (DECAF) score was calculated for predicting mortality. Multiplex polymerase chain reaction was carried out for respiratory viral assay from nasopharyngeal swabs, and sputum bacterial culture was also performed. Hospital mortality, invasive mechanical ventilation requirement, and length of hospital stay (LOS) were evaluated, and their associations with clinical characteristics, DECAF score, and serum biomarkers were examined. RESULTS: A total of 62 COPD patients were enrolled. These patients were classified as Global Initiative for Obstructive Lung Disease (GOLD) stage 2, 3, and 4 in 12.9%, 6.4%, and 80.7% of cases, respectively. Isolated bacterial exacerbation was recovered in 30.6% of exacerbation episodes: Klebsiella pneumoniae was the most commonly identified bacteria. Viral pathogens and coinfections were noted in 9.6% and 16.1% of exacerbated patients, respectively. Influenza was the most commonly detected viral pathogen. Serum biomarkers and DECAF score for viruses, bacteria, coinfection, and noninfectious causes of exacerbations were similar. Neither DECAF score nor serum biomarkers were able to differentiate patients with and without mortality or requiring mechanical ventilation. Increased serum PCT was noted in patients with LOS ≥7 days when compared with those with LOS <7 days (0.38 ng/mL vs 0.1 ng/mL; P=0.035). CONCLUSION: Increased serum PCT is associated with longer LOS in COPD exacerbation. However, CRP and DECAF score play limited roles in predicting clinical outcome and lack an association with causes of exacerbation.

Roles of roflumilast, a selective phosphodiesterase 4 inhibitor, in airway diseases.

Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases. Both diseases have incompletely distinct pathophysiology, clinical manifestation, and treatment responsiveness. Pulmonary and systemic inflammations are the hallmarks of COPD. Most asthma responds to inhaled corticosteroid (ICS) treatment. In contrast, COPD is a corticosteroid-resistant disease. Bronchodilators are a preferred treatment method of COPD, with the aim of improving symptoms and preventing exacerbation. In addition, corticosteroid insensitivity is an underlying mechanism in severe asthma. An overlap of features between asthma and COPD, which was described as asthma-COPD overlap syndrome (ACOS) is not uncommon in practice. Novel nonsteroidal therapies focusing on inflammation in asthma and COPD have been developed. Selective phosphodiesterase 4 (PDE4) inhibitor is a promising class of drugs that has been studied for the treatment of COPD. Selective PDE4 inhibitor is different from xanthine in terms of mechanisms and pharmacokinetic profiles. This review focuses on clinical data on PDE4 inhibitors and its future roles in asthma, COPD, bronchiectasis, ACOS and other chronic non-pulmonary diseases.

Peak inspiratory flow rate measurement by using In-Check DIAL for the different inhaler devices in elderly with obstructive airway diseases.

BACKGROUND: Inhaler device technique is a common cause of treatment failure in patients with asthma and chronic obstructive pulmonary disease. Dry powder inhaler (DPI) requires optimal peak inspiratory flow rate (PIFR) for drug delivery. Low PIFR generation is common in the elderly. Patient lung function and intrinsic inhaler resistance are factors for determining generated PIFR and drug delivery from DPI. OBJECTIVES: We aimed to identify the PIFR of the older (aged >60 years) and the younger (aged ≤60 years) patients with obstructive airway diseases for the different inhaler devices (Turbuhaler® and Accuhaler). PATIENTS AND METHODS: A cross-sectional study was conducted from January to December 2014. Patients with obstructive airway diseases were recruited. Spirometry was performed. PIFR was measured by using an In-Check DIAL device. Individual PIFR values for each inhaler device were obtained for three consecutive measurements and then averaged. RESULTS: A total of 139 patients diagnosed with obstructive lung diseases (asthma, n = 109; chronic obstructive pulmonary disease, n = 30) were recruited. Of these, 71 patients (51%) were >60 years. The PIFR generated by the patients who were ≤60 years for nonresistance mode was not different from that generated by those aged >60 years (115.0 ± 15.2 L/min vs 115.4 ± 13.3 L/min, p = 0.86). Regarding the DPI, PIFR generated from the older group was significantly lower than that generated from the younger group for Turbuhaler (72.5 ± 18.8 L/min vs 82.4 ± 21.1 L/min, p = 0.01), but the PIFR generated was not significantly different between the older and the younger groups for the Accuhaler (93.8 ± 22.9 L/min vs 99.4 ± 24.2 L/min, p = 0.86). The low peak expiratory flow rate and PIFR from spirometry were associated with the suboptimal PIFR measured by using In-Check DIAL. DISCUSSION: Optimal PIFR is critical for DPI use in the elderly; appropriate DPI selection is essential for management. In-Check DIAL may be useful for detecting inhaler device problem among the elderly. CONCLUSION: Lower PIFR generated from Turbuhaler was noted in patients with airway diseases who were older than 60 years, when compared to the younger patients.

Role of eosinophilic inflammation and atopy in elderly asthmatic patients.

BACKGROUND: Asthma in the elderly is severe and associated with poor treatment outcome. Although atopy has an important role in pathogenesis, its role in the elderly is unclear, partly due to immune senescence. OBJECTIVE: We aimed to examine the associations of Th2-mediated inflammation with asthma severity in the elderly. METHODS: Consecutive asthmatics older than 60 years without severe exacerbation within 8 weeks were enrolled. Atopic status was determined by positive serum specific IgE or skin prick test to common aeroallergens. Serum total IgE was measured simultaneously to exhaled fractional concentration of nitric oxide (FeNO). Asthma control level was assessed by using Thai Asthma Control Test (ACT) score. RESULTS: Total of 44 elderly asthmatic patients were enrolled. The mean age was 68.9 years and mean age of asthma diagnosis was 46.6 years. Seventy-seven percent of patients were female. Atopic status was found in 45.5% of patients. Uncontrolled asthma classified as ACT score < 20 was noted in 25% of elderly asthma, but its association with either high serum total IgE (≥120 IU/mL), high FeNO (≥50 ppb) or atopic status was not detected. CONCLUSION: One-fourth of elderly asthmatics were clinically uncontrolled, while atopy was confirmed in 45.5%. Neither high total IgE, high FeNO nor atopic status was associated with uncontrolled asthma in the elderly. Other factors might play role in asthma severity in the elderly, and has to be further investigated.

Validity and reliability of the Thai version of the leicester cough questionnaire in chronic cough.

BACKGROUND: Chronic cough is a common problem potentially disturbing the quality of life (QoL) of coughers. The Leicester Cough Questionnaire (LCQ), previously developed in England, is a validated, self-completed QoL instrument for assessment of chronic cough. This study aimed to develop a Thai version of the LCQ (LCQ-T) and assess its validity and reliability among adult Thai patients with subacute to chronic cough. METHODS: A total of 146 patients with a cough lasting for more than 3 weeks consented to participate in this study and self-administered the LCQ-T, together with the following 3 instruments: Borg Cough Scale (BCS), Short Form-36 (SF-36), and Hospital Anxiety Depression Scale (Thai-HADS). The LCQ-T was developed by applying a forward-backward translation approach. The LCQ-T comprises 19 items divided into 3 domains: physical (8 items), psychological (7 items), and social (4 items). To validate the LCQ-T, concurrent validity, internal consistency reliability, and test-retest reliability were assessed. RESULTS: Participants included 96 women and 50 men with a mean (SD) age of 59.6 (14.4) years. The concurrent validity comparing LCQ-T to BCS yielded statistically significant Pearson correlation coefficients (r= -0.74, P<0.05). The correlation coefficients for SF-36 and Thai-HADS were also significant. The LCQ-T demonstrated very good internal consistency in all domains and the overall scale, with the Cronbach's alpha coefficients ranging from 0.89 to 0.94. The 3-day repeatability of the LCQ-T in 25 clinically stable patients was high with the intra-class correlation coefficients ranging between 0.81 and 0.90. CONCLUSION: LCQ-T is a valid and reliable cough-specific instrument for assessing symptoms and QoL of adult Thai patients with subacute to chronic cough.