Explainable artificial intelligence for cough-related quality of life impairment prediction in asthmatic patients.

Explainable Artificial Intelligence (XAI) is becoming a disruptive trend in healthcare, allowing for transparency and interpretability of autonomous decision-making. In this study, we present an innovative application of a rule-based classification model to identify the main causes of chronic cough-related quality of life (QoL) impairment in a cohort of asthmatic patients. The proposed approach first involves the design of a suitable symptoms questionnaire and the subsequent analyses via XAI. Specifically, feature ranking, derived from statistically validated decision rules, helped in automatically identifying the main factors influencing an impaired QoL: pharynx/larynx and upper airways when asthma is under control, and asthma itself and digestive trait when asthma is not controlled. Moreover, the obtained if-then rules identified specific thresholds on the symptoms associated to the impaired QoL. These results, by finding priorities among symptoms, may prove helpful in supporting physicians in the choice of the most adequate diagnostic/therapeutic plan.

Exacerbation Burden in COPD and Occurrence of Mortality in a Cohort of Italian Patients: Results of the Gulp Study.

Objective: To describe the burden of moderate to severe exacerbations and all-cause mortality; the secondary objectives were to analyze treatment patterns and changes over follow-up. Design: Observational, multicenter, retrospective, cohort study with a three year follow-up period. Setting: Ten Italian academic secondary- and tertiary-care centers. Participants: Patients with a confirmed diagnosis of COPD referring to the outpatient clinics of the participating centers were retrospectively recruited. Primary and Secondary Outcome Measures: Annualized frequency of moderate and severe exacerbations stratified by exacerbation history prior to study enrollment. Patients were classified according to airflow obstruction, GOLD risk categories, and divided in 4 groups: A = no exacerbations; B = 1 moderate exacerbation; C = 1 severe exacerbation; D = ≥2 moderate and/or severe exacerbations. Overall all-cause mortality stratified by age, COPD category, and COPD therapy. A logistic regression model assessed the association of clinical characteristics with mortality. Results: 1111 patients were included (73% males), of which 41.5% had a history of exacerbations. As expected, the proportion of patients experiencing ≥1 exacerbation during follow-up increased according to pre-defined study risk categories (B: 79%, C: 84%, D: 97.4%). Overall, by the end of follow-up, 45.5% of patients without a history of exacerbation experienced an exacerbation (31% of which severe), and 13% died. Deceased patients were significantly older, more obstructed and hyperinflated, and more frequently active smokers compared with survivors. Severe exacerbations were more frequent in patients that died (23.5%, vs 10.2%; p-value: 0.002). Chronic heart failure and ischemic heart disease were the only comorbidities associated with a higher odds ratio (OR) for death (OR: 2.2, p-value: 0.001; and OR: 1.9, p-value: 0.007). Treatment patterns were similar in patients that died and survivors. Conclusion: Patients with a low exacerbation risk are exposed to a significant future risk of moderate/severe exacerbations. Real life data confirm the strong association between mortality and cardiovascular comorbidities in COPD.

Dupilumab Efficacy on Asthma Functional, Inflammatory, and Patient-Reported Outcomes across Different Disease Phenotypes and Severity: A Real-Life Perspective.

Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation.

Asthma and rhinitis control in adolescents and young adults: A real-world MASK-air study.

BACKGROUND: In allergic rhinitis and asthma, adolescents and young adult patients are likely to differ from older patients. We compared adolescents, young adults and adults on symptoms, control levels, and medication adherence. METHODS: In a cross-sectional study (2015-2022), we assessed European users of the MASK-air mHealth app of three age groups: adolescents (13-18 years), young adults (18-26 years), and adults (>26 years). We compared them on their reported rhinitis and asthma symptoms, use and adherence to rhinitis and asthma treatment and app adherence. Allergy symptoms and control were assessed by means of visual analogue scales (VASs) on rhinitis or asthma, the combined symptom-medication score (CSMS), and the electronic daily control score for asthma (e-DASTHMA). We built multivariable regression models to compare symptoms or medication accounting for potential differences in demographic characteristics and baseline severity. RESULTS: We assessed 965 adolescent users (15,252 days), 4595 young adults (58,161 days), and 15,154 adult users (258,796 days). Users of all three age groups displayed similar app adherence. In multivariable models, age groups were not found to significantly differ in their adherence to rhinitis or asthma medication. These models also found that adolescents reported lower VAS on global allergy, ocular, and asthma symptoms (as well as lower CSMS) than young adults and adults. CONCLUSIONS: Adolescents reported a better rhinitis and asthma control than young adults and adults, even though similar medication adherence levels were observed across age groups. These results pave the way for future studies on understanding how adolescents control their allergic diseases.

Moderate asthma: burden, mechanisms and therapeutic perspectives.

PURPOSE OF REVIEW: Global Initiative for Asthma (GINA) document provides a classification of asthma severity according with the current level of treatment required to achieve diseases control and underlines the limitations of this approach. In this review, we will provide an overview of recent investigations that have analyzed clinical and molecular features of moderate asthma. RECENT FINDINGS: Moderate asthma is heterogeneous in terms of response to inhaled treatment and pathogenetic mechanisms underlying the clinical features. Analysis of inflammatory pathways in patients who do not achieve disease remission allows identification of patient subgroups that may benefit from specific biological treatments. SUMMARY: Scientific progress makes increasingly clear that there are biological mechanisms capable of identifying and justifying the degree of severity of asthma. The identification of these, combined with the development of new pharmacological treatments, will be the cornerstones of improving the management of asthma in its degrees of severity.

BDP/FF NEXThaler to Improve Asthma Control Status in the Real World: The NEWTON Study.

In this article, we discuss the importance of real-world data in the treatment of patients with asthma and specifically the role of maintenance and reliever therapy (MART) with beclometasone dipropionate (BDP)/formoterol fumarate dihydrate (FF) delivered through a dry-powder inhaler (DPI) that contains an extrafine formulation. We also present the design of the NEWTON study. This multinational, multicenter, prospective, observational study will evaluate the real-world use of extrafine BDP/FF via a DPI as maintenance therapy and MART in patients with moderate to severe asthma. The study's primary outcome will be the proportion of patients improving their asthma control. Digitally collected patient-reported outcomes, such as the 5-item Asthma Control Questionnaire, the EuroQol 5-dimension 5-level, and the Test of the Adherence to Inhalers, will be used to assess the patient's asthma control, quality of life, and treatment adherence. Moreover, a new patient-reported outcome, the "Speed of change in health feeling" questionnaire, will be validated in a subgroup of patients. Overall, the results of this study will provide a real-life assessment of patients who perceived clinical benefits in a large cohort of asthmatics in Europe treated as per current clinical practice.

Personalized and Precision Medicine in Asthma and Eosinophilic Esophagitis: The Role of T2 Target Therapy.

The role of type 2 inflammation has been progressively associated with many diseases, including severe asthma, atopic dermatitis, nasal polyposis, eosinophilic granulomatosis with polyangiitis, and, recently, eosinophilic esophagitis. Despite this, the association between asthma and esophagitis is still poorly known, and this is probably because of the low prevalence of each disease and the even lower association between them. Nonetheless, observations in clinical trials and, subsequently, in real life, have allowed researchers to observe how drugs acting on type 2 inflammation, initially developed and marketed for severe asthma, could be effective also in treating eosinophilic esophagitis. For this reason, clinical trials specifically designed for the use of drugs targeted to type 2 inflammation were also developed for eosinophilic esophagitis. The results of clinical trials are presently promising and envisage the use of biologicals that are also likely to be employed in the field of gastroenterology in the near future. This review focuses on the use of biologicals for type 2 inflammation in cases of combined severe asthma and eosinophilic esophagitis.

Impulse oscillometry defined small airway dysfunction in asthmatic patients with normal spirometry: Prevalence, clinical associations, and impact on asthma control.

BACKGROUND: The small-airway dysfunction (SAD), detected with impulse oscillometry (IOS) methods, has been recently better characterized in patients with asthma. However, little is known about SAD in asthmatic patients with normal spirometry (NS). OBJECTIVE: In this study, we aimed to investigate, in an unselected sample of 321 patients with physician-diagnosed asthma and NS, prevalence, clinical characterization, and impact on asthma control of IOS-defined SAD. As a secondary objective of the study, we focused on comparing the difference between IOS- and spirometry-defined SAD. METHODS: Consecutive patients with a previous diagnosis of asthma but normal spirometry at the moment of the enrollment were stratified by the presence of IOS-defined SAD (difference in resistance at 5 Hz and at 20 Hz [R5-R20] greater than 0.07 kPa x s x L-1). We have also assessed the presence of SAD defined by spirometry, according to FEF 25-75 < 65% of the predicted. Clinical and laboratory features were collected, and univariable and multivariable analyses were used to analyze cross-sectional associations between clinical variables and outcomes (SAD). RESULTS: IOS-defined SAD was present in 54.1% of the cohort. In contrast, spirometry-defined SAD was present in only 10% of patients. Subjects with IOS-defined SAD showed less well-controlled asthma and a higher mean inhaled corticosteroid dosage use compared with subjects without SAD (both P < .001). Overweight (odds ratio [OR], 1.14; 95% CI, 1.05-1.23), exacerbation history (OR, 3.06; 95% CI, 1.34-6.97), asthma-related night awakenings (OR, 6.88; 95% CI, 2.13-22.23), exercise-induced asthma symptoms (OR, 33.5; 95% CI, 9.51-117.8), and controlled asthma (OR, 0.22; 95% CI, 0.06-0.84) were independently associated with SAD. CONCLUSIONS: Asthmatic patients with IOS-defined SAD showed less well-controlled asthma, more severe exacerbations and higher mean inhaled corticosteroid dosage. We confirmed exercise-induced asthma, asthma-related night awakenings, exacerbation history, and overweight as independently associated with SAD, while showing well-controlled asthma as inversely associated. SAD may be overlooked by standard spirometry.

Impairment of EQ-5D-5L Domains According to Allergic Rhinitis and Asthma Control: A MASK-air Real-World Study.

BACKGROUND: EQ-5D-5L (EuroQOL, 5 Domains, 5 Levels) is a widely used health-related quality-of-life instrument, comprising 5 domains. However, it is not known how each domain is impacted by rhinitis or asthma control. OBJECTIVE: To assess the association between rhinitis or asthma control and the different EQ-5D-5L domains using data from the MASK-air mHealth app. METHODS: In this cross-sectional study, we assessed data from all MASK-air users (2015-2021; 24 countries). For the levels of each EQ-5D-5L domain, we assessed rhinitis and asthma visual analog scales (VASs) and the combined symptom-medication score (CSMS). We built ordinal multivariable models assessing the adjusted association between VAS/CSMS values and the levels of each EQ-5D-5L domain. Finally, we compared EQ-5D-5L data from users with rhinitis and self-reported asthma with data from users with rhinitis alone. RESULTS: We assessed 5354 days from 3092 users. We observed an association between worse control of rhinitis or asthma (higher VASs and CSMS) and worse EQ-5D-5L levels. In multivariable models, all VASs and the CSMS were associated with higher levels of pain/discomfort and daily activities. For anxiety/depression, the association was mostly observed for rhinitis-related tools (VAS nose, VAS global, and CSMS), although the presence of self-reported asthma was also associated with worse anxiety/depression. Worse mobility ("walking around") was particularly associated with VAS asthma and with the presence of asthma. CONCLUSIONS: A worse rhinitis control and a worse asthma control are associated with higher EQ-5D-5L levels, particularly regarding pain/discomfort and activity impairment. Worse rhinitis control is associated with worse anxiety/depression, and poor asthma control with worse mobility.

The treatment of mild upper respiratory tract infections - a position paper with recommendations for best practice.

Following the waning severity of COVID-19 due to vaccination and the development of immunity, the current variants of SARS-CoV-2 often lead to mild upper respiratory tract infections (MURTIs), suggesting it is an appropriate time to review the pathogenesis and treatment of such illnesses. The present article reviews the diverse causes of MURTIs and the mechanisms leading to symptomatic illness. Different symptoms of MURTIs develop in a staggered manner and require targeted symptomatic treatment. A wide variety of remedies for home treatment is available, including over-the-counter drugs and plant-derived substances. Recent pharmacological research has increased the understanding of molecular effects, and clinical studies have shown the efficacy of certain herbal remedies. However, the use of subjective endpoints in these clinical studies may suggest limited validity of the results. In this position paper, the importance of patient-centric outcomes, including a subjective perception of improved well-being, is emphasized. A best practice approach for the management of MURTIs, in which pharmacists and physicians create an improved multi-professional healthcare setting and provide healthcare education to patients, is proposed. Pharmacists act as first-line consultants and provide patients with remedies, considering the individual patient's preferences towards chemical or plant-derived drugs and providing advice for self-monitoring. Physicians act as second-line consultants if symptoms worsen and subsequently initiate appropriate therapies. In conclusion, general awareness of MURTIs should be increased amongst medical professionals and patients, thus improving their management.

Criteria to evaluate efficacy of biologics in asthma: a Global Asthma Association survey.

BACKGROUND: Currently, there are no universally accepted criteria to measure the response to biologics available as treatment for severe asthma. This survey aims to establish consensus criteria to use for the evaluation of response to biologics after 4 months of treatment. METHOD: Using Delphi methodology, a questionnaire including 10 items was validated by 13 international experts in asthma. The electronic survey circulated within the Interasma Scientific Network platform. For each item, five answers were proposed graduated from 'no importance' to 'very high importance' and by a score (A = 2 points; B = 4 points; C = 6 points; D = 8 points; E = 10 points). The final criteria were selected if the median score for the item was ≥7 and > 60% of responses according 'high importance' and 'very high importance'. All selected criteria were validated by the experts. RESULTS: Four criteria were identified: reduce daily systemic corticosteroids dose by ≥50%; decrease the number of asthma exacerbations requiring systemic corticosteroids by ≥50%; have no/minimal side effects; and obtain asthma control according validated questionnaires. The consensual decision was that ≥3 criteria define a good response to biologics. CONCLUSIONS: Specific criteria were defined by an international panel of experts and could be used as tool in clinical practice.

Patient-centered digital biomarkers for allergic respiratory diseases and asthma: The ARIA-EAACI approach - ARIA-EAACI Task Force Report.

Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.

Digital Coaching Using Smart Inhaler Technology to Improve Asthma Management in Patients With Asthma in Italy: Community-Based Study.

BACKGROUND: Reliance on short-acting ß-2 agonists and nonadherence to maintenance medication are associated with poor clinical outcomes in asthma. Digital health solutions could support optimal medication use and therefore disease control in patients with asthma; however, their use in community settings has not been determined. OBJECTIVE: The primary objective of this study is to investigate community implementation of the Turbu+ program designed to support asthma self-management, including adherence to budesonide and formoterol (Symbicort) Turbuhaler, a combination inhaler for both maintenance therapy or maintenance and reliever therapy. The secondary objective is to provide health care professionals with insights into how patients were using their medication in real life. METHODS: Patients with physician-diagnosed asthma were prescribed budesonide and formoterol as maintenance therapy, at a dose of either 1 inhalation twice daily (1-BID) or 2 inhalations twice daily (2-BID), or as maintenance and reliever therapy (1-BID and reliever or 2-BID and reliever in a single inhaler), and they received training on Turbu+ in secondary care centers across Italy. An electronic device attached to the patients' inhaler for ≥90 days (data cutoff) securely uploaded medication use data to a smartphone app and provided reminders, visualized medication use, and motivational nudge messages. Average medication adherence was defined as the proportion of daily maintenance inhalations taken as prescribed (number of recorded maintenance actuations per day or maintenance inhalations prescribed per day) averaged over the monitoring period. The proportion of adherent days was defined as the proportion of days when all prescribed maintenance inhalations were taken on a given day. The Wilcoxon test was used to compare the proportion of adherent days between patients in the maintenance regimen and patients in the maintenance and reliever regimen of a given dose. RESULTS: In 661 patients, the mean (SD) number of days monitored was 217.2 (SD 109.0) days. The average medication adherence (maintenance doses taken/doses prescribed) was 70.2% (108,040/153,820) overall and was similar across the groups (1-BID: 6332/9520, 66.5%; 1­BID and reliever: 43,578/61,360, 71.0%; 2-BID: 10,088/14,960, 67.4%; 2-BID and reliever: 48,042/67,980, 70.7%). The proportion of adherent days (prescribed maintenance doses/doses taken in a given day) was 56.6% (31,812/56,175) overall and was higher with maintenance and reliever therapy (1-BID and reliever vs 1-BID: 18,413/30,680, 60.0% vs 2510/4760, 52.7%; P<.001; 2-BID and reliever vs 2-BID: 8995/16,995, 52.9% vs 1894/3740, 50.6%; P=.02). Rates of discontinuation from the Turbu+ program were significantly lower with maintenance and reliever therapy compared with maintenance therapy alone (P=.01). CONCLUSIONS: Overall, the high medication adherence observed during the study might be attributed to the electronic monitoring and feedback mechanism provided by the Turbu+ program.

Might Dog Walking Reduce the Impact of COPD on Patients' Life?

Low levels of physical activity (PA) lead to a worsening of physical condition and contributes to multimorbidity in Chronic Obstructive Respiratory Disease (COPD). Unsupervised PA related to dog ownership may contribute to reducing sedentary behavior. We aimed to investigate the relationship between dog walking, patient-reported outcomes (PROs) and exacerbations in COPD. A pre-defined sample of 200 COPD patients (dog owners and non-dog owners) with symptomatic COPD was sourced from a database representative of the Italian population. A computer-assisted personal interview was used to assess health status impairment (CAT), fatigue (FACIT), health-related quality of life (HRQoL) (EQ-5D), and PA frequency. In the whole sample, PA was associated with better CAT, EQ-5D, VAS, FACIT scores and reduced number of exacerbation (p < 0.001). Under the same CAT scores, dog-walking duration was associated with a better HRQoL (EQ5D, p = 0.015) and less fatigue (FACIT, p = 0.017). In an adjusted regression model, walking dogs >30 min was associated with lower fatigue (FACIT) than having no dogs and walking dogs <15 min (p = 0.026 and p = 0.009, respectively). Motivation related to dog walking could modify patients' tendency to focus on symptoms during PA and, therefore, to perceive the fatigue. Dog walking may be effective for increasing and maintaining regular PA, reducing the subjective impact of COPD.

Correction: Digital Coaching Using Smart Inhaler Technology to Improve Asthma Management in Patients With Asthma in Italy: Community-Based Study.

[This corrects the article DOI: 10.2196/25879.].

Real-world data using mHealth apps in rhinitis, rhinosinusitis and their multimorbidities.

Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real-time, real-world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK-air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients.

The 5T approach in asthma: Triple Therapy Targeting Treatable Traits.

Using a therapeutic strategy that is free from traditional diagnostic labels and based on the identification of "treatable traits" (TTs), which are influential in clinical presentations in each patient, might overcome the difficulties in identifying and validating asthma phenotypes and endotypes. Growing evidence is documenting the importance of using the triple therapy with ICS, LABA, and LAMAs in a single inhaler (SITT) in cases of asthma not controlled by ICS/LABA and in the prevention of exacerbations. The identification of TTs may overcome the possibility of using SITT without considering the specific needs of the patient. In effect, it allows a treatment strategy that is closer to the precision strategy now widely advocated for the management of patients with asthma. There are different TTs in asthma that may benefit from treatment with SITT, regardless of guideline recommendations. The airflow limitation and small airway dysfunction are key TTs that are present in different phenotypes/endotypes, do not depend on the degree of T2 inflammation, and respond better than other treatments to SITT. We suggest that the 5T (Triple Therapy Targeting Treatable Traits) approach should be applied to the full spectrum of asthma, not just severe asthma, and, consequently, SITT should begin earlier than currently recommended.

Personalized Management of Patients with Chronic Rhinosinusitis with Nasal Polyps in Clinical Practice: A Multidisciplinary Consensus Statement.

Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5-15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current standards of care. Biologics are an emerging treatment option for patients with severe uncontrolled CRSwNP, but their positioning in the treatment algorithm is under discussion. Effective endotyping of CRSwNP patients who could benefit from biologics treatment is required, as suggested by international guidelines. Other issues affecting management include comorbidities, such as allergy, non-steroidal anti-inflammatory drug-exacerbated respiratory disease, and asthma. Therefore, the choice of treatment in CRSwNP patients depends on many factors. A multidisciplinary approach may improve CRSwNP management in patients with comorbidities, but currently there is no shared management model. We summarize the outcomes of a Delphi process involving a multidisciplinary panel of otolaryngologists, pulmonologists, and allergist-immunologists involved in the management of CRSwNP, who attempted to reach consensus on key statements relating to the diagnosis, endotyping, classification and management (including the place of biologics) of CRSwNP patients.

Future Perspectives of Revaluating Mild COPD.

In 2020, COPD was the third leading cause of death worldwide. Lung function is central for the diagnosis of this disease, and COPD severity is still partially classified based on airflow obstruction, which can range from "mild" (GOLD 1 group, FEV1 ≥80% predicted) to "very severe" (GOLD 4, FEV1 <30% predicted). However, the term "mild COPD" needs to be carefully analyzed. Several studies have shown that even in the presence of a mild obstruction, patients can have significant symptoms, physiological deterioration, evidence of emphysema, and suffer from recurrent exacerbations. Small airways pathology significantly correlates with the presence of symptoms, and it has been demonstrated that the onset of bronchiolitis occurs earlier than that of emphysema. These damages have long been known to not be detectable with conventional tests, and exclusive reliance on spirometry is not enough to adequately study and stage a patient with "mild COPD." Therefore, early identification of COPD is of utmost importance in the light of modifying the natural course of the disease. However, patients with early lung damage are yet to be included and studied in interventional clinical trials.