Predictors of persistent poor control and validation of ASSESS score: Longitudinal 5-year follow-up of severe asthma cohort.

Background: Longitudinal predictors of persistent poor asthma control in severe asthma (SA) cohort remain scarce. The predictive value of the asthma severity scoring system (ASSESS) in the SA cohort outside the original study and in the Asian population is unknown. Objective: We sought to determine the 5-year longitudinal outcome of patients with SA and validate the use of ASSESS score in predicting future outcomes in SA. Methods: A prospective longitudinal observational study of patients with SA attending the multidisciplinary specialist SA clinic of the Singapore General Hospital from 2011 to 2021 was conducted. The number of exacerbations and asthma control test results were recorded yearly for 5 consecutive years. The ASSESS score was computed at baseline, and the area under the receiver-operating characteristic curve for predicting persistent poor asthma control was generated. Results: Of the 489 patients recruited into the study, 306 patients with 5-year follow-up data were analyzed. Seventy-three percent had type 2 inflammation with increased overall exacerbations over 5 years (rate ratio, 2.55; 95% CI, 1.31-4.96; P = .006) relative to non-type 2 SA. In the multivariate model, bronchiectasis, gastroesophageal reflux disease, and an asthma control test score of less than 20 were significantly associated with persistent poor asthma control over 5 years. ASSESS scores were good at predicting persistent poor asthma control with an area under the receiver-operating characteristic curve of 0.71 (95% CI, 0.57-0.84). Conclusions: Bronchiectasis and gastroesophageal reflux disease are predictors for persistent poor asthma control and targeted traits for precision medicine in SA. The ASSESS score has a good prediction for persistent poor asthma control over 5 years.

Trait profiles in difficult-to-treat asthma: Clinical impact and response to systematic assessment.

BACKGROUND: Multidisciplinary systematic assessment improves outcomes in difficult-to-treat asthma, but without clear response predictors. Using a treatable-traits framework, we stratified patients by trait profile, examining clinical impact and treatment responsiveness to systematic assessment. METHODS: We performed latent class analysis using 12 traits on difficult-to-treat asthma patients undergoing systematic assessment at our institution. We examined Asthma Control Questionnaire (ACQ-6) and Asthma Quality of Life Questionnaire (AQLQ) scores, FEV1 , exacerbation frequency, and maintenance oral corticosteroid (mOCS) dose, at baseline and following systematic assessment. RESULTS: Among 241 patients, two airway-centric profiles were characterized by early-onset with allergic rhinitis (n = 46) and adult onset with eosinophilia/chronic rhinosinusitis (n = 60), respectively, with minimal comorbid or psychosocial traits; three non-airway-centric profiles exhibited either comorbid (obesity, vocal cord dysfunction, dysfunctional breathing) dominance (n = 51), psychosocial (anxiety, depression, smoking, unemployment) dominance (n = 72), or multi-domain impairment (n = 12). Compared to airway-centric profiles, non-airway-centric profiles had worse baseline ACQ-6 (2.7 vs. 2.2, p < .001) and AQLQ (3.8 vs. 4.5, p < .001) scores. Following systematic assessment, the cohort showed overall improvements across all outcomes. However, airway-centric profiles had more FEV1 improvement (5.6% vs. 2.2% predicted, p < .05) while non-airway-centric profiles trended to greater exacerbation reduction (1.7 vs. 1.0, p = .07); mOCS dose reduction was similar (3.1 mg vs. 3.5 mg, p = .782). CONCLUSION: Distinct trait profiles in difficult-to-treat asthma are associated with different clinical outcomes and treatment responsiveness to systematic assessment. These findings yield clinical and mechanistic insights into difficult-to-treat asthma, offer a conceptual framework to address disease heterogeneity, and highlight areas responsive to targeted intervention.

Interval change in fractional exhaled nitric oxide (FENO) reflects short-term change in adherence following electronic inhaler reminders.

BACKGROUND: In asthma, suppression of fractional exhaled nitric oxide (FENO) is a marker of adherence in the short-term. The usefulness of FENO to indicate change in adherence in the longer term is unknown. The aims of this study were to determine the relationship between changes in adherence and corresponding changes in FENO over short (1 week) and long-term (3 month) periods. METHODS: After establishing initial ICS adherence using electronic inhaler monitor (EIM) devices, reminders were switched on for 1 week ('short-term') to optimize adherence. Reminders were then switched off and patients followed up after 3 months ('long-term'). FENO was measured at the start and end of each period. Using linear regression, we analyzed change in FENO in relation to change in adherence. RESULTS: Forty-two patients contributed complete data for analysis. In the short-term, change in adherence was independently associated with change in FENO (ß = -0.36, p = 0.036) even after adjusting for initial adherence and ICS dose. The higher the initial FENO, the greater the decline in FENO with improved adherence. This relationship between change in adherence and change in FENO was not observed in the long-term. CONCLUSION: Change in adherence over 1 week following the use of EIM reminders independently predicted change in FENO. This relationship was not maintained at 3 months.

Nebulizer versus metered dose inhaler with space chamber (MDI spacer) for acute asthma and chronic obstructive pulmonary disease exacerbation: attitudes of patients and healthcare providers in the COVID-19 era.

OBJECTIVE: Short-acting bronchodilators for asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly delivered by nebulizers although administration using metered dose inhaler with space chamber (MDI spacer) has been shown to be equally efficacious. There are few studies examining patients' and healthcare providers' attitudes on the two administration methods in adults. This study explores patients' and healthcare providers' attitudes on the use of nebulizer versus MDI spacer for acute asthma and COPD exacerbations in adults. METHODS: Patients admitted for asthma or COPD exacerbations, doctors, and nurses in a university-affiliated hospital were surveyed from 1 April 2021 to 30 September 2021 regarding their views on the effectiveness, ease of use, preparation and administration, side effects, and infection risk of the two administration methods. RESULTS: Ninety-nine patients, 103 doctors, and 650 nurses completed the survey. 60.6% of patients perceived nebulizer to be more effective. Patients who found nebulizer more comfortable were more likely to prefer nebulizer (OR 43.97, p = 0.01), while those who associated it with a greater infection risk were less likely to prefer nebulizer (OR 0.15, p = 0.03). 49.5% of doctors and 49.1% of nurses perceived nebulizer to be more effective, compared to 10.7% and 34.5%, respectively, for MDI spacer. Effectiveness and patient comfort influenced doctors' and nurses' preference for nebulizer while ease of preparation and administration influenced nurses' preference only. CONCLUSIONS: Patients and healthcare providers perceived nebulizer to be more effective. Factors unique to each group influenced their preference for nebulizer.

Assessing the cost-effectiveness of mepolizumab as add-on therapy to standard of care for severe eosinophilic asthma in Singapore.

OBJECTIVE: To evaluate the cost-effectiveness of mepolizumab added to standard of care (SOC) compared with SOC alone among patients with severe uncontrolled eosinophilic asthma in the Singapore setting. METHODS: A Markov model with three health states (asthma on mepolizumab and SOC, asthma on SOC alone, and death) was developed from a healthcare system perspective over a lifetime horizon. During each 4-week cycle, patients in the non-death health states could experience asthma exacerbations requiring oral corticosteroid burst, emergency department visit, or hospitalization. Asthma-related mortality following an exacerbation or all-cause mortality could also occur at each cycle. The model was populated using local costs while utilities were derived from international literature. Transition probabilities were obtained from a mixture of Singapore-specific and internationally published data. RESULTS: The base-case analysis comparing mepolizumab plus SOC with SOC alone resulted in an incremental cost-effectiveness ratio (ICER) of SGD335 486 (USD238 195) per quality-adjusted life-year (QALY) gained. Sensitivity analysis demonstrated that the ICER was most sensitive to the price of mepolizumab, followed by the proportion of exacerbations which required hospital intensive care. Despite restricting mepolizumab use to patients with a higher baseline exacerbation rate (3 in the past year) in a scenario analysis, the ICER remained high at SGD238 876 (USD 169 602) per QALY gained. CONCLUSION: At its current price, mepolizumab is not considered a cost-effective use of healthcare resources in Singapore. Substantial price reductions for mepolizumab are required to improve its cost-effectiveness to an acceptable range. These results will be useful to inform national funding decisions.

A risk prediction score to identify patients at low risk for COVID-19 infection.

Introduction: Singapore's enhanced surveillance programme for COVID-19 identifies and isolates hospitalised patients with acute respiratory symptoms to prevent nosocomial spread. We developed risk prediction models to identify patients with low risk for COVID-19 from this cohort of hospitalised patients with acute respiratory symptoms. Methods: This was a single-centre retrospective observational study. Patients admitted to our institution's respiratory surveillance wards from 10 February to 30 April 2020 contributed data for analysis. Prediction models for COVID-19 were derived from a training cohort using variables based on demographics, clinical symptoms, exposure risks and blood investigations fitted into logistic regression models. The derived prediction models were subsequently validated on a test cohort. Results: Of the 1,228 patients analysed, 52 (4.2%) were diagnosed with COVID-19. Two prediction models were derived, the first based on age, presence of sore throat, dormitory residence, blood haemoglobin level (Hb), and total white blood cell counts (TW), and the second based on presence of headache, contact with infective patients, Hb and TW. Both models had good diagnostic performance with areas under the receiver operating characteristic curve of 0.934 and 0.866, respectively. Risk score cut-offs of 0.6 for Model 1 and 0.2 for Model 2 had 100% sensitivity, allowing identification of patients with low risk for COVID-19. Limiting COVID-19 screening to only elevated-risk patients reduced the number of isolation days for surveillance patients by up to 41.7% and COVID-19 swab testing by up to 41.0%. Conclusion: Prediction models derived from our study were able to identify patients at low risk for COVID-19 and rationalise resource utilisation.

Laryngeal hypersensitivity and abnormal cough response during mannitol bronchoprovocation challenge.

BACKGROUND AND OBJECTIVE: Inhalational challenge with dry mannitol powder may potentially induce cough by two mechanisms: airway bronchoconstriction or laryngeal irritation. This prospective observational study investigated laryngeal and bronchial components of cough induced by mannitol challenge. METHODS: We recruited consecutive patients referred for clinical mannitol challenge. The Newcastle Laryngeal Hypersensitivity Questionnaire (LHQ) was administered. Throughout testing, coughs were audio-recorded to derive a cough frequency index per time and dose of mannitol. Relationships between cough indices, laryngeal hypersensitivity and bronchial hyperresponsiveness (BHR) were examined. Participants were classified by cough characteristics with k-means cluster analysis. RESULTS: Of 90 patients who underwent challenge, 83 completed both the questionnaire and challenge. Cough frequency was greater in patients with abnormal laryngeal hypersensitivity (p = 0.042), but not in those with BHR. There was a moderate negative correlation between coughs per minute and laryngeal hypersensitivity score (r = -0.315, p = 0.004), with lower LHQ scores being abnormal. Cluster analysis identified an older, female-predominant cluster with higher cough frequency and laryngeal hypersensitivity, and a younger, gender-balanced cluster with lower cough frequency and normal laryngeal sensitivity. CONCLUSION: Cough frequency during mannitol challenge in our cohort reflected laryngeal hypersensitivity rather than BHR. Laryngeal hypersensitivity was more often present among older female patients. With the incorporation of cough indices, mannitol challenge may be useful to test for laryngeal hypersensitivity as well as BHR.

Diagnostic and Therapeutic Outcomes Following Systematic Assessment of Patients with Concurrent Suspected Vocal Cord Dysfunction and Asthma.

BACKGROUND: Vocal cord dysfunction (VCD) is present in 25% to 50% of patients with asthma. When both diagnoses are suspected, accurate diagnosis and targeted management represent a clinical challenge. OBJECTIVE: To evaluate diagnostic and therapeutic outcomes following systematic assessment for patients with concurrent suspected VCD and asthma. METHODS: Patients underwent systematic evaluation by clinical assessment and validated questionnaires, followed by multidisciplinary management. VCD was confirmed by visualization of paradoxical vocal fold motion at baseline or following provocation. Asthma was confirmed by demonstrating variable airflow obstruction. Asthma medications were deescalated in those with low clinical probability of asthma and no variable airflow obstruction. Response to 2 or more sessions of speech pathology was assessed by subjective report and standardized questionnaires. RESULTS: Among 212 consecutive patients, 62 (29%) patients had both VCD and asthma, 54 (26%) had VCD alone, 51 (24%) had asthma alone, and 45 (21%) had neither. Clinician assessment and the Laryngeal Hypersensitivity Questionnaire both predicted laryngoscopy-confirmed VCD. Deescalation or discontinuation of asthma therapy was possible in 37 of 59 (63%) patients without variable airflow obstruction, and was most successful (odds ratio, 5.5) in the presence of laryngoscopy-confirmed VCD (25 of 31, or 81%) Patients with VCD responded subjectively to 2 or more sessions of speech pathology, but laryngeal questionnaire scores did not improve. CONCLUSIONS: Expert clinician assessment and the Laryngeal Hypersensitivity Questionnaire predict the presence of laryngoscopy-confirmed VCD. Systematic assessment for both VCD and asthma facilitates deescalation or discontinuation of unnecessary asthma medications. Subjective symptom improvement following speech pathology was not paralleled by laryngeal questionnaire scores in this cohort.

Electronic Inhaler Monitoring for Chronic Airway Disease: Development and Application of a Multidimensional Efficacy Framework.

Inhaled therapy is the cornerstone of chronic airway disease therapy, but poor adherence to controller inhalers worsens clinical outcomes and increases cost. Monitoring of controller use is needed to improve adherence, and monitoring of reliever use can predict impending exacerbations. Both can be accurately achieved by electronic inhaler monitoring (EIM). However, evidence for EIM use in clinical practice is limited and varied, and knowledge gaps remain across different outcomes and health settings. We aimed to develop a framework to assess EIM systematically across all aspects of efficacy, apply this framework to the current literature, and identify gaps in efficacy to inform future development in the field. We adapted an existing framework for diagnostic tests, consisting of six levels of efficacy with ascending clinical relevance: technical, diagnostic accuracy, diagnostic thinking, therapeutic, patient outcome, and societal efficacy. Tailoring this framework to EIM, we incorporated expert feedback and applied it to the EIM efficacy literature. We found that EIM has good diagnostic accuracy, diagnostic thinking, and therapeutic efficacies, but evidence is lacking for specific aspects of technical, patient outcome, and societal efficacies. Further development of EIM requires improved reliability, usability, and data security for patients, and optimal integration with electronic medical records and overall patient care. Defining appropriate target patient groups and pairing EIM data with effective interventions, in conjunction with reducing costs through technological innovation and economies of scale, will enhance patient and societal outcome efficacies.

Paradoxical Vocal Fold Motion in Difficult Asthma Is Associated with Dysfunctional Breathing and Preserved Lung Function.

BACKGROUND: Many patients with difficult asthma also have coexisting vocal cord dysfunction (VCD), evident by paradoxical vocal fold motion (PVFM) on laryngoscopy. OBJECTIVE: Among patients with difficult asthma, we sought to identify clinical features associated with laryngoscopy-diagnosed PVFM. METHODS: Consecutive patients with "difficult asthma" referred by respiratory specialists underwent systematic assessment in this observational study. Those with a high clinical suspicion for VCD were referred for laryngoscopy, either at rest or after mannitol provocation. Statistical analyses were performed to identify clinical factors associated with PVFM, and a multivariate logistic regression model was fitted to control for confounders. RESULTS: Of 169 patients with difficult asthma, 63 (37.3%) had a high clinical probability of VCD. Of 42 who underwent laryngoscopy, 32 had PVFM confirmed. Patients with PVFM more likely had preserved lung function (prebronchodilator forced expiratory ratio 74% ± 11 vs 62% ± 16, P < .001); physiotherapist-confirmed dysfunctional breathing (odds ratio [OR] = 5.52, 95% confidence interval [CI]: 2.4-12.7, P < .001), gastro-oesophageal reflux (OR = 2.6, 95% CI: 1.16-5.8, P = .02), and a lower peripheral eosinophil count (0.09 vs 0.23, P = .004). On multivariate logistic regression, independent predictors for PVFM were dysfunctional breathing (OR = 4.93, 95% CI: 2-12, P < .001) and preserved lung function (OR = 1.07, 95% CI: 1.028-1.106, P < .001). CONCLUSION: Among specialist-referred patients with difficult asthma, VCD pathogenesis may overlap with dysfunctional breathing but is not associated with severe airflow obstruction. Dysfunctional breathing and preserved lung function may serve as clinical clues for the presence of VCD.

Systematic Assessment of Difficult-to-Treat Asthma: Principles and Perspectives.

Difficult-to-treat asthma affects a minority of adults and children with asthma but represents a challenging mix of misdiagnosis, multimorbidity, inadequate self-management, severe airway pathobiology, and treatment complications. Management of these patients extends beyond asthma pharmacotherapy, because multiple other patient-related domains need to be addressed as well. Such complexity can hinder adequate clinical assessment even when performed in specialist practice. Systematic assessment undertaken by specialized multidisciplinary teams brings a broad range of resources to bear on patients with difficult-to-treat asthma. Although the concept of systematic assessment is not new, practices vary considerably and implementation is not universal. Nevertheless, assessment protocols are already in place in several institutions worldwide, and outcomes after such assessments have been highly encouraging. This review discusses the rationale, components, and benefits of systematic assessment, outlining its clinical utility and the available evidence for improved outcomes. It describes a range of service configurations and assessment approaches, drawing examples from severe asthma centers around the world to highlight common essential elements. It also provides a framework for establishing such services and discusses practical considerations for implementation.

Addressing the impact of ethnicity on asthma care.

PURPOSE OF REVIEW: In asthma, there is an increasing focus on personalizing treatment by targeting treatable traits. Ethnicity has effects on many biological and behavioural traits, and so is an important consideration when personalizing asthma care. This review has particular relevance in light of current patterns of international migration, which are leading to unprecedented levels of ethnic heterogeneity in many geographic regions. RECENT FINDINGS: This review examines the effect of ethnicity on three key domains - biological traits, behavioural traits and health system behaviour. Ethnicity influences asthma biology by affecting biomarker reference ranges, response to drug therapy and asthma phenotypes. Ethnicity impacts behavioural traits through its effects on psychosocial well being, adherence and asthma self-management. Ethnic minorities are often disadvantaged with regards to healthcare access and healthcare interactions. SUMMARY: Concerted action is needed to address current issues around behavioural traits and healthcare behaviour, which are influenced by ethnicity. More research is required to understand the impact of ethnicity on asthma biology, especially the interplay between genetic and environmental influences on asthma, and the differential response to asthma therapies.

Asthma phenotypes in a multi-ethnic Asian cohort.

BACKGROUND: Identification of asthma phenotypes facilitates our understanding of asthma pathobiologies. Phenotypes observed in homogenous Asian cohorts have distinct differences from those described in Caucasian cohorts, suggesting that ethnicity may influence phenotypic expression. Phenotypic clusters in a multi-ethnic Southeast Asian cohort have not been described before, and direct comparisons of these clusters within a single study may reveal how ethnicity affects phenotypic expression. METHODS: Six hundred and thirty adult asthma patients from two healthcare institutions in Singapore were randomly assigned in a 2:1 fashion to a test and validation cohort. Latent class analysis was performed on both cohorts using age of asthma onset, sex, ethnicity, smoking status, body mass index, lung function, blood eosinophil count, asthma control test score, and exacerbation frequency as input variables. Phenotypic clusters between the test and validation cohorts were compared RESULTS: Three clusters were identified in both the test and validation cohorts, with corresponding clusters of each cohort sharing similar characteristics. Ethnic representation and asthma control were significantly different between clusters. Cluster one comprised Chinese females with late-onset asthma and the best asthma control. Cluster two comprised non-Chinese females with obesity and the worst asthma control. Cluster three was multi-ethnic with the greatest proportion of atopic patients. CONCLUSION: We identified three phenotypic clusters in our multi-ethnic Southeast Asian population, with distinct differences in ethnicity which may be attributable to inherent differences in baseline characteristics among ethnic groups.

Blood eosinophil count correlates with severity of respiratory failure in life-threatening asthma and predicts risk of subsequent exacerbations.

BACKGROUND: An elevated blood eosinophil count when asthma is stable predicts exacerbations and therapeutic response to corticosteroids or biologics targeting eosinophils. Few studies have examined the prognostic value of blood eosinophils measured at exacerbation. AIM: To elucidate the relationship between a spot blood eosinophil count-measured at the onset of a life-threatening asthma exacerbation-with indices of exacerbation severity and risk of subsequent exacerbations. METHODS: Real-world, retrospective review of all life-threatening asthma cases admitted at 4 public hospitals in Singapore between 2011-2015. We assessed the trends and correlations between blood eosinophil count on admission with arterial blood gas values, duration of mechanical ventilation, and risk of death, hypoxic ischemic encephalopathy or respiratory arrest. Risk of future exacerbations among survivors was modelled using Cox regression and survival curves. RESULTS: There were 376 index life-threatening exacerbations with median blood eosinophil count (5-95th percentiles) of 0.270 × 109 /L (0-1.410 × 109 /L). Arterial pH decreased and PCO2 increased with increasing eosinophil count. Duration of mechanical ventilation and risk of death, hypoxic ischaemic encephalopathy or respiratory arrest did not vary with eosinophils. Among 329 survivors who were followed-up over a median of 52 months, blood eosinophils ≥1.200 × 109 /L was associated with an increased hazard of emergency visits and/or admissions for asthma (hazard ratio 1.8, 95% confidence interval 1.1-2.9, P = .02). CONCLUSION: In this study of life-threatening asthma, we found that a spot blood eosinophil count correlates with severity of respiratory failure and predicts risk of subsequent exacerbations.

Predictors of future exacerbations in a multi-ethnic Asian population with asthma.

OBJECTIVE: Exacerbations are important outcomes in asthma. Risk factors for exacerbations may differ in different populations. Although various demographic and clinical variables were examined in previous studies on exacerbation risks in asthma, important variables such as ethnicity, adherence, and medication titration were not included. This study examined independent predictors of future exacerbations in a multi-ethnic asthma population in Asia, while including the variables of ethnicity, medication adherence, and medication change in our analysis. METHODS: We recruited patients with physician-diagnosed asthma in a tertiary hospital in Singapore over a one-year period. Exacerbations requiring ≥3 days of systemic corticosteroids one year prior to study enrolment (previous exacerbations) and the year following enrolment (future exacerbations) were recorded from electronic medical records. Medication adherence was based on pharmacy refill. An increase or a decrease in the Global Initiative for Asthma treatment steps were considered to be medication up- and down-titration, respectively. A multivariate logistic regression model was constructed to determine independent predictors of future exacerbations. RESULTS: The study cohort of 340 patients comprised mainly of Chinese (53.2%), Malay (32.9%), and Indian (9.7%) ethnicities. After multivariate analysis, only Indian ethnicity (OR 3.75, 95% CI 1.077-13.051, p = 0.038), Asthma Control Test score (OR 0.913, 95% CI 0.839-0.995, p = 0.037), and the number of previous exacerbations (OR 1.84, 95% CI 1.416-2.391, p < 0.001) were independent predictors of future exacerbations. CONCLUSIONS: There are ethnic differences in exacerbation risk in Asian populations. Each incremental worsening of the asthma symptom control score and each additional exacerbation also increases the risk of future exacerbations.

Diagnosis of severe asthma.

Patients with asthma that is uncontrolled despite high intensity medication can present in both primary and specialist care. An increasing number of novel (and expensive) treatments are available for patients who fail conventional asthma therapy, but these may not be appropriate for all such patients. It is essential that a rigorous evaluation process be undertaken for these patients to identify those with biologically severe asthma who will require novel therapies, and those who may improve with control of contributory factors. In this article, we describe three key steps in the diagnostic evaluation process for severe asthma. The first step is confirmation of asthma diagnosis with objective evidence of variable airflow obstruction. The second involves management of contributory factors such as non-adherence, poor inhaler technique, ongoing asthma triggers, and comorbidities. The third step involves phenotyping and endotyping of patients with severe asthma. We provide a practical approach to implementing these measures in both primary and secondary care.

Recent developments and highlights in biomarkers in allergic diseases and asthma.

The potential of precision medicine in allergy and asthma has only started to be explored. A significant clarification in the pathophysiology of rhinitis, chronic rhinosinusitis, asthma, food allergy and drug hypersensitivity was made in the last decade. This improved understanding led to a better classification of the distinct phenotypes and to the discovery of new drugs such as biologicals, targeting phenotype-specific mechanisms. Nevertheless, many conditions remain poorly understood such as non-eosinophilic airway diseases or non-IgE-mediated food allergy. Moreover, there is a need to predict the response to specific therapies and the outcome of drug and food provocations. The identification of patients at risk of progression towards severity is also an unmet need in order to establish adequate preventive or therapeutic measures. The implementation of precision medicine in the clinical practice requires the identification of phenotype-specific markers measurable in biological matrices. To become useful, these biomarkers need to be quantifiable by reliable systems, and in samples obtained in an easy, rapid and cost-efficient way. In the last years, significant research resources have been put in the identification of valid biomarkers for asthma and allergic diseases. This review summarizes these recent advances with focus on the biomarkers with higher clinical applicability.