ERS statement on transition of care in childhood interstitial lung diseases.

Interstitial lung diseases (ILD) are a heterogeneous group of rare diffuse diseases affecting the lung parenchyma in children and adults. Childhood interstitial lung diseases (chILD) are often diagnosed at very young age, affect the developing lung, and can have different presentations and prognosis compared to adult forms of these diseases. Also, chILD in many cases may apparently remit, and have a better response to therapy and better prognosis than adult ILD. Many affected children will reach adulthood with minimal activity or clinical remission of the disease. They need continuing care and follow-up from childhood to adulthood if the disease persists and progresses over time but also if they are asymptomatic and in full remission. Therefore, for every chILD patient an active transition process from paediatric to adult care should be guaranteed. This ERS statement provides a review of the literature and current practice concerning transition of care in chILD. It draws on work in existing transition care programs in other chronic respiratory diseases, disease-overarching transition of care programs, evidence on the impact of these programs on clinical outcomes, current evidence regarding long-term remission of chILD as well as the lack of harmonisation between the current adult ILD and chILD classifications impacting on transition of care. While the transition system is well established in several chronic diseases, such as cystic fibrosis or diabetes mellitus, we could not find sufficient published evidence on transition systems in chILD. This statement summarises current knowledge but cannot yet provide evidence-based recommendations for clinical practice.

Expression of PD-1/PD-L1 axis in mediastinal lymph nodes and lung tissue of human and experimental lung fibrosis indicates a potential therapeutic target for idiopathic pulmonary fibrosis.

BACKGROUND: Mediastinal lymph node enlargement is prevalent in patients with idiopathic pulmonary fibrosis (IPF). Studies investigating whether this phenomenon reflects specific immunologic activation are lacking. METHODS: Programmed cell death-1 (PD-1)/ programmed cell death ligand-1 (PD-L1) expression in mediastinal lymph nodes and lung tissues was analyzed. PD-1, PD-L1 mRNA expression was measured in tracheobronchial lymph nodes of mice following bleomycin-induced injury on day 14. Finally, the effect of the PD-1 inhibitor, pembrolizumab, in bleomycin-induced pulmonary fibrosis was investigated. RESULTS: We analyzed mediastinal lymph nodes of thirty-three patients (n = 33, IPF: n = 14, lung cancer: n = 10, concomitant IPF and lung cancer: n = 9) and lung tissues of two hundred nineteen patients (n = 219, IPF: 123, controls: 96). PD-1 expression was increased, while PD-L1 expression was decreased, in mediastinal lymph nodes of patients with IPF compared to lung cancer and in IPF lungs compared to control lungs. Tracheobronchial lymph nodes isolated on day 14 from bleomycin-treated mice exhibited increased size and higher PD-1, PD-L1 mRNA levels compared to saline-treated animals. Pembrolizumab blunted bleomycin-induced lung fibrosis, as indicated by reduction in Ashcroft score and improvement in respiratory mechanics. CONCLUSIONS: Mediastinal lymph nodes of patients with IPF exhibit differential expression profiles than those of patients with lung cancer indicating distinct immune-mediated pathways regulating fibrogenesis and carcinogenesis. PD-1 expression in mediastinal lymph nodes is in line with lung tissue expression. Lower doses of pembrolizumab might exert antifibrotic effects. Clinical trials aiming to endotype patients based on mediastinal lymph node profiling and accordingly implement targeted therapies such as PD-1 inhibitors are greatly anticipated.

Psoriatic Insomnia: A Subjective and Objective Sleep Evaluation.

Psoriasis may affect patients' sleep. In order to examine this relationship, this study evaluated non-anxious and non-depressive patients with moderate to severe psoriasis before and after 6 months of systemic treatment. A prospective case-control study with 46 consecutive patients (mean age 51.1 ± 12.8 years, 18 women) and 24 age-, sex- and body mass index-matched controls (mean age 46.5 ± 15.4 years, 12 women) was conducted to assess sleep using both sleep questionnaires and actigraphy. Of psoriatic patients, 91.3% were poor sleepers, and 65.2% of the psoriatic patients presented insomnia symptoms, compared with 54.2% and 33.3% of the control group (p < 0.001, p = 0.02, respectively). Actigraphy showed that Total Sleep Time was shorter in patients, while 82.6% of the psoriatic patients had poor Sleep Efficiency, compared with controls (p = 0.004, p = 0.03, respectively). Patients' quality of life was associated with sleep disturbance (p < 0.001), and pruritus was negatively correlated with sleep duration (p < 0.001). After 6 months of treatment, patients' sleep pattern, according to actigraphy, had not changed significantly; however, they had insomnia for no longer than the control group (p = 0.65), whereas the above-mentioned correlations were non-significant after treatment. Psoriatic insomnia was improved after 6 months of systemic treatment. Actigraphy may be used as an objective tool to evaluate sleep in these patients.

ABCA3-related interstitial lung disease beyond infancy.

BACKGROUND: The majority of patients with childhood interstitial lung disease (chILD) caused by pathogenic variants in ATP binding cassette subfamily A member 3 (ABCA3) develop severe respiratory insufficiency within their first year of life and succumb to disease if not lung transplanted. This register-based cohort study reviews patients with ABCA3 lung disease who survived beyond the age of 1 year. METHOD: Over a 21-year period, patients diagnosed as chILD due to ABCA3 deficiency were identified from the Kids Lung Register database. 44 patients survived beyond the first year of life and their long-term clinical course, oxygen supplementation and pulmonary function were reviewed. Chest CT and histopathology were scored blindly. RESULTS: At the end of the observation period, median age was 6.3 years (IQR: 2.8-11.7) and 36/44 (82%) were still alive without transplantation. Patients who had never received supplemental oxygen therapy survived longer than those persistently required oxygen supplementation (9.7 (95% CI 6.7 to 27.7) vs 3.0 years (95% CI 1.5 to 5.0), p=0.0126). Interstitial lung disease was clearly progressive over time based on lung function (forced vital capacity % predicted absolute loss -1.1% /year) and on chest CT (increasing cystic lesions in those with repetitive imaging). Lung histology pattern were variable (chronic pneumonitis of infancy, non-specific interstitial pneumonia, and desquamative interstitial pneumonia). In 37/44 subjects, the ABCA3 sequence variants were missense variants, small insertions or deletions with in-silico tools predicting some residual ABCA3 transporter function. CONCLUSION: The natural history of ABCA3-related interstitial lung disease progresses during childhood and adolescence. Disease-modifying treatments are desirable to delay such disease course.

Lung cancer in patients with idiopathic pulmonary fibrosis: A retrospective multicentre study in Europe.

BACKGROUND AND OBJECTIVE: There remains a paucity of large databases for patients with idiopathic pulmonary fibrosis (IPF) and lung cancer. We aimed to create a European registry. METHODS: This was a multicentre, retrospective study across seven European countries between 1 January 2010 and 18 May 2021. RESULTS: We identified 324 patients with lung cancer among 3178 patients with IPF (prevalence = 10.2%). By the end of the 10 year-period following IPF diagnosis, 26.6% of alive patients with IPF had been diagnosed with lung cancer. Patients with IPF and lung cancer experienced increased risk of all-cause mortality than IPF patients without lung cancer (HR: 1.51, [95% CI: 1.22-1.86], p < 0.0001). All-cause mortality was significantly lower for patients with IPF and lung cancer with a monocyte count of either <0.60 or 0.60-<0.95 K/µl than patients with monocyte count ≥0.95 K/µl (HR [<0.60 vs. ≥0.95 K/µl]: 0.35, [95% CI: 0.17-0.72], HR [0.60-<0.95 vs. ≥0.95 K/µl]: 0.42, [95% CI: 0.21-0.82], p = 0.003). Patients with IPF and lung cancer that received antifibrotics presented with decreased all cause-mortality compared to those who did not receive antifibrotics (HR: 0.61, [95% CI: 0.42-0.87], p = 0.006). In the adjusted model, a significantly lower proportion of surgically treated patients with IPF and otherwise technically operable lung cancer experienced all-cause mortality compared to non-surgically treated patients (HR: 0.30 [95% CI: 0.11-0.86], p = 0.02). CONCLUSION: Lung cancer exerts a dramatic impact on patients with IPF. A consensus statement for the management of patients with IPF and lung cancer is sorely needed.

Sestrin 2 levels are associated with emphysematous phenotype of COPD.

Sestrins (Sesns) are a family of highly conserved stress-inducible proteins and various stresses have been shown to strongly up-regulate them. Sestrin 2 (Sesn2) deficiency has been shown to partially suppress pulmonary emphysema. The aim of this study was to evaluate Sesn2 levels in COPD patients and its possible associations with the presence of emphysema and blood eosinophils. All patients underwent lung function testing and high-resolution computed tomography (HRCT) of the chest. The presence of emphysematous lesions in >15% of the pulmonary parenchyma was considered as significant emphysema. Sixty-seven patients were included in the study. 40/67 patients were characterized as having significant emphysema. Patients with significant emphysema had higher levels of Sesn2 (ng/ml) [median (IQR) 6.7 (2.7,10.3 vs 1.09 (0.9,1.9), p<0.001)] and significantly lower % and absolute blood eosinophil counts (cells/µL) compared to patients without emphysema [1 (0, 2) vs 4 (2, 4) p<0.001 and 62 (0, 110) vs 248 (180, 300), p<0.001 respectively]. Sesn2 presented a significant positive correlation to the score of emphysema in HRCT (rs = 0.87, p<0.001) and similar positive but weaker correlation to FRC (rs = 0.27, p = 0.024). Negative correlations were observed between Sesn2 and either the % of blood eosinophils and/or the absolute blood eosinophil count (rs = -0.79, p<0.001, and rs = -0.78, p<0.001 respectively). Sesn2 levels above 1.87 ng/ml showed a high diagnostic performance for the presence of significant emphysema in HRCT with an AUC 0.93, 95% CI (0.85,0.98), p<0.001. Sesn2 could serve as a potential biomarker of emphysema.

SARS-Cov-2 Infection in Severe Asthma Patients Treated With Biologics.

BACKGROUND: At the beginning of the pandemic, there have been considerable concerns regarding coronavirus disease 2019 (COVID-19) severity and outcomes in patients with severe asthma treated with biologics. OBJECTIVE: To prospectively observe a cohort of severe asthmatics treated with biologics for the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and disease severity during the COVID-19 pandemic. METHODS: Physicians from centers treating patients with severe asthma all over Greece provided demographic and medical data regarding their patients treated with biologics. Physicians were also asked to follow up patients during the pandemic and to perform a polymerase chain reaction test in case of a suspected SARS-Cov-2 infection. RESULTS: Among the 591 severe asthmatics (63.5% female) included in the study, 219 (37.1%) were treated with omalizumab, 358 (60.6%) with mepolizumab, and 14 (2.4%) with benralizumab. In total, 26 patients (4.4%) had a confirmed SARS-CoV-2 infection, 9 (34.6%) of whom were admitted to the hospital because of severe COVID-19, and 1 required mechanical ventilation and died 19 days after admission. Of the 26 infected patients, 5 (19.2%) experienced asthma control deterioration, characterized as exacerbation that required treatment with systemic corticosteroids. The scheduled administration of the biological therapy was performed timely in all patients with the exception of 2, in whom it was postponed for 1 week according to their doctors' suggestion. CONCLUSION: Our study confirms that despite the initial concerns, SARS-CoV-2 infection is not more common in asthmatics treated with biologics compared with the general population, whereas the use of biologic treatments for severe asthma during the COVID-19 pandemic does not seem to be related to adverse outcomes from severe COVID-19.

Paucigranulocytic Asthma: Potential Pathogenetic Mechanisms, Clinical Features and Therapeutic Management.

Asthma is a heterogeneous disease usually characterized by chronic airway inflammation, in which several phenotypes have been described, related to the age of onset, symptoms, inflammatory characteristics and treatment response. The identification of the inflammatory phenotype in asthma is very useful, since it allows for both the recognition of the asthmatic triggering factor as well as the optimization of treatment The paucigranulocytic phenotype of asthma (PGA) is characterized by sputum eosinophil levels <1−3% and sputum neutrophil levels < 60%. The precise characteristics and the pathobiology of PGA are not fully understood, and, in some cases, it seems to represent a previous eosinophilic phenotype with a good response to anti-inflammatory treatment. However, many patients with PGA remain uncontrolled and experience asthmatic symptoms and exacerbations, irrespective of the low grade of airway inflammation. This observation leads to the hypothesis that PGA might also be either a special phenotype driven by different kinds of cells, such as macrophages or mast cells, or a non-inflammatory phenotype with a low grade of eosinophilic inflammation. In this review, we aim to describe the special characteristics of PGA and the potential therapeutic interventions that could be offered to these patients.

Reduced immunogenicity of the mRNA vaccine BNT162b2 in patients with idiopathic pulmonary fibrosis.

Patients with #IPF do not mount appreciable anti-spike antibody responses to two doses of #SARSCoV2 mRNA vaccine compared to the general population. National authorities should prioritise patients with IPF for booster doses. https://bit.ly/3K2KXQ0.

Epidemiological characteristics and outcomes from 187 patients with COVID-19 admitted to 6 reference centers in Greece: an observational study during the first wave of the COVID-19 pandemic.

INTRODUCTION: Epidemiological data from patients with COVID-19 has been recently published in several countries. Nationwide data of hospitalized patients with COVID-19 in Greece remain scarce. MATERIAL AND METHODS: This was an observational, retrospective study from 6 reference centers between February 26 and May 15, 2020. RESULTS: The patients were mostly males (65.7%) and never smokers (57.2%) of median age 60 (95% CI: 57.6-64) years. The majority of the subjects (98%) were treated with the standard-of-care therapeutic regimen at that time, including hydroxychlo-roquine and azithromycin. Median time of hospitalization was 10 days (95% CI: 10-12). Twenty-five (13.3%) individuals were intubated and 8 died (4.2%). The patients with high neutrophil-to-lymphocyte ratio (NLR) ( > 3.58) exhibited more severe disease as indicated by significantly increased World Health Organization (WHO) R&D ordinal scale (4; 95% CI: 4-4 vs 3; 95% CI: 3-4, p = 0.0001) and MaxFiO2% (50; 95% CI: 38.2-50 vs 29.5; 95% CI: 21-31, p < 0.0001). The patients with increased lactate dehydrogenase (LDH) levels ( > 270 IU/ml) also exhibited more advanced disease compared to the low LDH group ( < 270 IU/ml) as indicated by both WHO R&D ordinal scale (4; 95% CI: 4-4 vs 4; 95% CI: 3-4, p = 0.0001) and MaxFiO2% (50; 95% CI: 35-60 vs 28; 95% CI: 21-31, p < 0.0001). CONCLUSION: We present the first epidemiological report from a low-incidence and mortality COVID-19 country. NLR and LDH may represent reliable disease prognosticators leading to timely treatment decisions.

Increased monocyte count and red cell distribution width as prognostic biomarkers in patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) represents a chronic lung disease with unpredictable course. METHODS: We aimed to investigate prognostic performance of complete blood count parameters in IPF. Treatment-naïve patients with IPF were retrospectively enrolled from two independent cohorts (derivation and validation) and split into subgroups (high and low) based on median baseline monocyte count and red cell distribution width (RDW). RESULTS: Overall, 489 patients (derivation cohort: 300, validation cohort: 189) were analyzed. In the derivation cohort, patients with monocyte count ≥ 0.60 K/µL had significantly lower median FVC%pred [75.0, (95% CI 71.3-76.7) vs. 80.9, (95% CI 77.5-83.1), (P = 0.01)] and DLCO%pred [47.5, (95% CI 44.3-52.3) vs. 53.0, (95% CI 48.0-56.7), (P = 0.02)] than patients with monocyte count < 0.60 K/µL. Patients with RDW ≥ 14.1% had significantly lower median FVC%pred [75.5, (95% CI 71.2-79.2) vs. 78.3, (95% CI 76.0-81.0), (P = 0.04)] and DLCO%pred [45.4, (95% CI 43.3-50.5) vs. 53.0, (95% CI 50.8-56.8), (P = 0.008)] than patients with RDW < 14.1%. Cut-off thresholds from the derivation cohort were applied to the validation cohort with similar discriminatory value, as indicated by significant differences in median DLCO%pred between patients with high vs. low monocyte count [37.8, (95% CI 35.5-41.1) vs. 45.5, (95% CI 41.9-49.4), (P < 0.001)] and RDW [37.9, (95% CI 33.4-40.7) vs. 44.4, (95% CI 41.5-48.9), (P < 0.001)]. Patients with high monocyte count and RDW of the validation cohort exhibited a trend towards lower median FVC%pred (P = 0.09) and significantly lower median FVC%pred (P = 0.001), respectively. Kaplan-Meier analysis in the derivation cohort demonstrated higher all-cause mortality in patients with high (≥ 0.60 K/µL) vs. low monocyte count (< 0.60 K/µL) [HR 2.05, (95% CI 1.19-3.53), (P = 0.01)]. CONCLUSIONS: Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF.

Long-term efficacy and safety of omalizumab in patients with allergic asthma: A real-life study.

Background: The efficacy and safety of omalizumab in patients with severe allergic asthma have been established in both randomized controlled trials and real-life studies. Objective: To evaluate the sustained effectiveness and safety of long-term treatment with omalizumab in a real-world setting. Methods: In this retrospective study, we included patients treated with omalizumab for at least 8 years in four asthma clinics in Greece. Pulmonary function, asthma control, oral corticosteroids (OCS) dose, and exacerbations were recorded before treatment, 6 months later, and annually thereafter. Adverse events were also recorded. Results: Forty-five patients (66.7% women), mean ± standard deviation (SD) age 55.3 ± 12.2 years, were included. The duration of treatment with omalizumab was 10.6 ± 1.2 years. The annual exacerbation rate decreased from 4.1 before omalizumab initiation to 1.1 after 1 year of treatment and remained low up to the 8th year of treatment (p < 0.001). From the 19 patients who were receiving OCS at baseline, 21.1% patients discontinued after 6 months, 47.4% were still on OCS after 4 years of therapy, and 31.6% were on OCS after 8 years. With regard to the OCS dose, 36.8% of the patients reduced the dose ≥ 50% after 6 months and 68.4% achieved 50% reduction after 2 years. The mean daily OCS dose before omalizumab initiation was 7.8 mg of prednisolone or the equivalent, reduced to 4.7 mg/day after 6 months, which reached 1.6 mg/day after 8 years (p < 0.001). Treatment with omalizumab resulted in significant improvements of asthma control and lung function. No severe adverse events were reported. Conclusion: In this real-life study, omalizumab resulted in significant and sustained improvements in asthma exacerbations, asthma control, and lung function, and had a steroid sparing effect and a good safety profile.

Device use errors among patients with asthma and COPD and the role of training: a real-life study.

Background and objectives: Administration of inhaled medication for asthma and COPD is often difficult and incorrect device use is associated with unfavorable outcomes. We aimed to evaluate device use errors in asthma and COPD patients and to associate incorrect use with the patient's characteristics and medical history.Methods: Demographics and medical history were recorded. The use of each prescribed device was evaluated according to predefined steps.Results: 607 patients (49.9% male, median age (IQR) 63 (51, 70) years performed 663 demonstrations (56 patients were using 2 different types of devices). 51.4% were treated for asthma and 48.6% for COPD. 79.6% of demonstrations were performed using DPIs. Errors were documented on 41.2% of demonstrations and were associated with the type of device, p < 0.001. Elderly patients were less frequently using their devices correctly compared to younger patients, 50.8% vs 62.2%, respectively, p = 0.007. Correct demonstrations were more among asthmatics compared to COPD patients 63.1% vs 54.5%, p = 0.024. Incorrect use was associated with more acute exacerbations in the preceding year [median(IQR), 1(0, 2) vs 1(0, 1)], for incorrect and correct use, respectively, p < 0.001. Upon demonstration, 15.5% of patients have never been trained (i.e., undergone actual demonstrations and observation while using their device) by anyone. Errors occurred more frequently among patients who reported not to be trained compared to those who were trained, 67.0% vs 14.6%, respectively, p < 0.001. The commonest error was associated with the inspiration maneuver and accounted for the 48.3% of errors in the DPIs and 53.0% of errors in the MDIs.Conclusion: Device use errors are common and associated with unfavorable outcomes. Trained patients were more likely to use the device correctly.

Switching between biologics in severe asthma patients. When the first choice is not proven to be the best.

During the last decades, new treatments targeting disease mechanisms referred as biologics have been introduced in the therapy of asthma and currently, five monoclonal antibodies have been approved. Although these therapeutic agents have been formulated to target specific asthma endotypes, it is often difficult for the treating physician to identify which patient is the best candidate for each one of these specific treatments especially in the clinical scenario of a patient in whom clinical characteristics overlap between different endotypes, allowing the selection of more than one biologic agent. As no head-to-head comparisons between these biologics have been attempted, there is no evidence on the superiority of one biologic agent over the other. Furthermore, a physician's first therapeutic decision, no matter how carefully has been made, may often result in suboptimal clinical response and drug discontinuation, indicating the need for switching to a different biologic. In this short review, we discuss the available evidence regarding the switching between biologics in patients with severe asthma and we propose a simple algorithm on switching possibilities in case that the physicians' initial choice is proven not to be the best.

Economic Burden and Management of Systemic Sclerosis-Associated Interstitial Lung Disease in 8 European Countries: The BUILDup Delphi Consensus Study.

INTRODUCTION: Systemic sclerosis (SSc) is a rare chronic autoimmune disease characterised by microvascular damage, immune dysregulation and fibrosis, affecting the skin, joints and internal organs. Interstitial lung disease (ILD) is frequently associated with systemic sclerosis (SSc-ILD), leading to a poor prognosis and a high mortality rate. The aim of the BUILDup study (BUrden of Interstitial Lung Disease Consensus Panel) was to investigate the overall disease management and to estimate the social and economic burden of SSc-ILD across 8 European countries. METHODS: A modified Delphi method was used to obtain information on the management of SSc-ILD patients among 40 specialists (panellists) from 8 European countries. Average annual costs per patient and country were estimated by means of a direct cost-analysis study. RESULTS: The panellists had managed 805 SSc-ILD patients in the last year, 39.1% with limited (L-SSc-ILD) and 60.9% with extensive (E-SSc-ILD) disease. Of these, 32.8% of the panellists started treatment at diagnosis, 42.3% after signs of deterioration/progression and 24.7% when the disease had become extensive. The average annual cost of SSc-ILD per patient ranged from €6191 in Greece to €25,354 in Sweden. Main cost drivers were follow-up procedures, accounting for 80% of the total annual costs. Hospitalisations were the most important cost driver of follow-up costs. Healthcare resource use was more important for E-SSc-ILD compared to L-SSc-ILD. Early retirement was taken by 40.4% of the patients with an average of 11.9 years before the statutory retirement age. CONCLUSIONS: SSc-ILD entails not only a clinical but also a social and economic burden, and is higher for E-SSc-ILD.

The Burden of Progressive Fibrosing Interstitial Lung Disease: A DELPHI Approach.

INTRODUCTION: The term progressive fibrosing interstitial lung disease (ILD) describes patients with fibrotic ILDs who, irrespective of the aetiology of the disease, show a progressive course of their disease despite current available (and non-licensed) treatment. Besides in idiopathic pulmonary fibrosis, little is known about management and the burden of patients with fibrotic ILD, particularly those with a progressive behaviour. METHODS: Using the Delphi method, 40 European experts in ILD management delivered information on management of (progressive) fibrosing ILD and on the impact of the disease on patients' quality of life (QoL) and healthcare resource utilisation (HCRU). Annual costs were calculated for progressive and non-/slow-progressive fibrosing ILD for diagnosis, follow-up management, exacerbation management, and end-of-life care based on the survey data. RESULTS: Physicians reported that progression in fibrosing ILD worsens QoL in both patients and their caregivers. Progression of fibrosing ILD was associated with a greater use of HCRU for follow-up visits and maintenance treatment compared with the non-/slow progression. The number of patients who suffered at least one acute exacerbation was reported to be more than three times higher in progressive fibrosing ILD patients than in patients with non-/slow-progressive fibrosing ILD. On average, annual estimated costs of progressive fibrosing ILD per patient were 1.8 times higher than those of the non-/slow-progressive form of the disease. CONCLUSIONS: Progression in fibrosing ILD causes a significant impact on QoL and HCRU and costs. These survey data underline the need for safe and effective therapies to slow the disease progression.

Sirtuin 1: Endocan and Sestrin 2 in Different Biological Samples in Patients with Asthma. Does Severity Make the Difference?

BACKGROUND: Sestrin 2, Endocan, and Sirtuin 1 are distinct molecules with some biologic actions associated with asthma pathophysiology. The aim of the present study was to determine the molecular level differences attributable to underlying asthma severity. METHODS: We initially recruited 85 asthmatics with a wide spectrum of severity. All of the patients were optimally treated according to current guidelines. Demographics, test results of lung function, and treatment regimes of all patients were recorded. Sestrin 2, Endocan, and Sirtuin 1 were measured in different biological samples (sputum with two processing methods and serum). RESULTS: A total of 60 patients (35 with severe asthma) were analyzed, since 25 patients failed to produce an adequate sample of sputum. Patients with severe asthma showed significantly higher values for Sestrin 2 [pg/mL], measured in both sputum supernatant and cell pellet, compared to those with mild to moderate asthma [9524 (5696, 12,373) vs. 7476 (4265, 9273) p = 0.029, and 23,748 (15,280, 32,742) vs. 10,084 (3349, 21,784), p = 0.008, respectively]. No other significant differences were observed. No significant associations were observed between biomarkers, inflammatory cells, and lung function. CONCLUSION: Sestrin 2 is increased in patients with severe asthma as part of a mechanism that may modify structural alterations through the imbalance between oxidative stress and antioxidant activity.