The Role of Galectins in Asthma Pathophysiology: A Comprehensive Review.

Galectins are a group of ß-galactoside-binding proteins with several roles in immune response, cellular adhesion, and inflammation development. Current evidence suggest that these proteins could play a crucial role in many respiratory diseases such as pulmonary fibrosis, lung cancer, and respiratory infections. From this standpoint, an increasing body of evidence have recognized galectins as potential biomarkers involved in several aspects of asthma pathophysiology. Among them, galectin-3 (Gal-3), galectin-9 (Gal-9), and galectin-10 (Gal-10) are the most extensively studied in human and animal asthma models. These galectins can affect T helper 2 (Th2) and non-Th2 inflammation, mucus production, airway responsiveness, and bronchial remodeling. Nevertheless, while higher Gal-3 and Gal-9 concentrations are associated with a stronger degree of Th-2 phlogosis, Gal-10, which forms Charcot-Leyden Crystals (CLCs), correlates with sputum eosinophilic count, interleukin-5 (IL-5) production, and immunoglobulin E (IgE) secretion. Finally, several galectins have shown potential in clinical response monitoring after inhaled corticosteroids (ICS) and biologic therapies, confirming their potential role as reliable biomarkers in patients with asthma.

Short-term Tezepelumab effectiveness in patients with severe asthma: a multicenter study.

OBJECTIVE: Severe asthma presents significant management challenges, often requiring advanced treatments to control symptoms and reduce exacerbations. The use of monoclonal antibodies has revolutionized the clinical course of patients with severe asthma, showing a significant impact on exacerbations reduction, oral corticosteroids (OCS) cessation and on the improvement of lung function and quality of life. Tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody, has emerged as a potential therapeutic option for these patients. METHODS: We conducted an observational, prospective, multicenter study including 20 patients with confirmed severe asthma according to ERS guidelines and GINA recommendations. Patients received Tezepelumab 210 mg every 4 wk due to uncontrolled asthma despite maximal inhalation treatment with ICS/LABA. Data were collected before treatment initiation (T0) and after three months from the first administration (T3). RESULTS: After three months of Tezepelumab treatment, we reported significant improvements in asthma symptoms and quality of life, as well as a consistent reduction in exacerbations and OCS use. We found no statistically meaningful differences among main clinical and functional outcomes according to inflammatory biomarkers, while lung function improved significantly in patients with less allergic sensitization. No serious adverse event was reported during the follow up, while the rates of mild adverse effects were comparable to those from registration trials. CONCLUSION: Tezepelumab demonstrated short-term efficacy in improving asthma control and quality of life, showing a favorable safety profile. Further studies with larger sample sizes and longer follow-up would confirm these findings and identify predictors of response to Tezepelumab.

The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. Rises in the epithelial barrier permeability of airways alter tissue homeostasis and allow the penetration of allergens and other external agents. Different factors contribute to barrier impairment, such as eosinophilic infiltration and allergen protease action-eosinophilic cationic proteins' effects and allergens' proteolytic activity both contribute significantly to epithelial damage. In the airways, allergen proteases degrade the epithelial junctional proteins, allowing allergen penetration and its uptake by dendritic cells. This increase in allergen-immune system interaction induces the release of alarmins and the activation of type 2 inflammatory pathways, causing or worsening the main symptoms at the skin, bowel, and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic protease-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance, and progression. Moreover, we will explore potential clinical and radiological biomarkers of airway remodeling in allergic asthma patients.

Electronic Nose Analysis of Exhaled Breath Volatile Organic Compound Profiles during Normoxia, Hypoxia, and Hyperoxia.

This study investigates volatile organic compound (VOC) profiles in the exhaled breath of normal subjects under different oxygenation conditions-normoxia (FiO2 21%), hypoxia (FiO2 11%), and hyperoxia (FiO2 35%)-using an electronic nose (e-nose). We aim to identify significant differences in VOC profiles among the three conditions utilizing principal component analysis (PCA) and canonical discriminant analysis (CDA). Our results indicate distinct VOC patterns corresponding to each oxygenation state, demonstrating the potential of e-nose technology in detecting physiological changes in breath composition (cross-validated accuracy values: FiO2 21% vs. FiO2 11% = 63%, FiO2 11% vs. FiO2 35% = 65%, FiO2 21% vs. FiO2 35% = 71%, and p < 0.05 for all). This research underscores the viability of breathomics in the non-invasive monitoring and diagnostics of various respiratory and systemic conditions.

Can single-inhaler Beclometasone Dipropionate/Formoterol Fumarate/Glycopyrronium therapy postpone or save biologics for severe asthma?

Inhaled corticosteroids, along with beta2-agonists and anti-muscarinics, represent the cornerstone of asthma treatment. Although the advent of monoclonal antibodies has dramatically changed severe asthma management, there are still patients ineligible or with poor response to biologics. Moreover, high costs associated with monoclonal antibodies prescription are still an open issue, leading clinicians to carefully assess cost-benefit ratio before their administration. From this perspective, the use of single-inhaler Beclometasone Dipropionate/Formoterol Fumarate/Glycopyrronium in patients with severe asthma could not only improve their clinical and functional performance, but also postpone biologic prescription, with positive repercussions on healthcare costs.

Effect of Food Intake on Exhaled Volatile Organic Compounds Profile Analyzed by an Electronic Nose.

Exhaled breath analysis using an e-nose is a groundbreaking tool for exhaled volatile organic compound (VOC) analysis, which has already shown its applicability in several respiratory and systemic diseases. It is still unclear whether food intake can be considered a confounder when analyzing the VOC-profile. We aimed to assess whether an e-nose can discriminate exhaled breath before and after predefined food intake at different time periods. We enrolled 28 healthy non-smoking adults and collected their exhaled breath as follows: (a) before food intake, (b) within 5 min after food consumption, (c) within 1 h after eating, and (d) within 2 h after eating. Exhaled breath was collected by a formerly validated method and analyzed by an e-nose (Cyranose 320). By principal component analysis, significant variations in the exhaled VOC-profile were shown for principal component 1 (capturing 63.4% of total variance) when comparing baseline vs. 5 min and vs. 1 h after food intake (both p < 0.05). No significance was shown in the comparison between baseline and 2 h after food intake. Therefore, the exhaled VOC-profile seems to be influenced by very recent food intake. Interestingly, two hours might be sufficient to avoid food induced alterations of exhaled VOC-spectrum when sampling for research protocols.

Assessment of Five Questionnaires for Chronic Obstructive Pulmonary Disease in a Southern Italian Population: A Proof-of-Concept Study.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is a growing burden to society, and remains underdiagnosed in Italy. This study aimed at evaluating five validated screening questionnaires to consider which one was the most accurate, and the optimal cut-off score for each to be considered for the Southern Italian population. Materials and Methods: A total of 144 patients were recruited in the study. The age range was 46-85 years. All subjects underwent spirometry, and completed the five questionnaires: CDQ, LFQ, COPD-PS, COPD-SQ, and CAPTURE. Receiver-operator curves (ROC) were drawn for each questionnaire. The area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), values for the optimal cut-off score and previously recommended score were calculated and compared. Results: Of the questionnaires, the CDQ, LFQ, and COPD-SQ had significant differences between COPD (n = 86) and non-COPD (n = 52) groups. The AUCs for each questionnaire with (95%CI) were: CAPTURE, 0.602 (0.431-0.773); CDQ, 0.714 (0.555-0.872); LFQ, 0.331 (0.183-0.479; COPD-PS, 0.652 (0.497-0.807); and COPD-SQ, 0.679 (0.520-0.837). Only the CDQ and COPD-SQ had significant AUC screening characteristics. The optimal cut-off values for the CDQ, LFQ, and COPD-PS were modified to 22, 10, and 4, respectively. The COPD-SQ remained at 17. Conclusion: The CDQ and COPD-SQ can discriminate between individuals with and without COPD in the Italian population. The CDQ has a moderate screening accuracy, and the COPD-PS and COPD-SQ have low accuracy, when the optimal cut-off scores are used. Of the five questionnaires assessed, the CDQ and COPD-SQ questionnaires could be used for screening for COPD in the Southern Italian population.

The Role of a Polymer-Based E-Nose in the Detection of Head and Neck Cancer from Exhaled Breath.

The aim of our study was to assess whether a polymer-based e-nose can distinguish head and neck cancer subjects from healthy controls, as well as from patients with allergic rhinitis. A total number of 45 subjects participated in this study. The first group was composed of 15 patients with histology confirmed diagnosis of head and neck cancer. The second group was made up of 15 patients with diagnoses of allergic rhinitis. The control group consisted of 15 subjects with a negative history of upper airways and/or chest symptoms. Exhaled breath was collected from all participants and sampled by a polymer-based e-nose (Cyranose 320, Sensigent, Pasadena, CA, USA). In the Principal Component Analysis plot, patients with head and neck cancer clustered distinctly from the controls as well as from patients with allergic rhinitis. Using canonical discriminant analysis, the three groups were discriminated, with a cross validated accuracy% of 75.1, p < 0.01. The area under the curve of the receiver operating characteristic curve for the discrimination between head and neck cancer patients and the other groups was 0.87. To conclude, e-nose technology has the potential for application in the diagnosis of head and neck cancer, being an easy, quick, non-invasive and cost-effective tool.

Relationships between Obstructive Sleep Apnea Syndrome and cardiovascular risk in a naïve population of southern Italy.

BACKGROUND: Obstructive sleep apnea (OSA) is a worldwide increasing syndrome, which, by promoting endothelial dysfunction, contributes to extend the cardiovascular risk. We evaluated the cardiovascular risk in a group of OSA patients. METHODS: A total of 185 OSA subjects (19 normal weight, 57 overweight, 109 obese), who entered the Ambulatory of Sleep Disorders of the Institute of Respiratory Diseases of the University of Bari, during 1 year, were enrolled in the study. We assessed anthropometric features, polysomnographic findings, cardiovascular risk factors, smoking habit, Pulmonary Function Test, Arterial Blood Gas Analysis, Epworth Questionnaire, and Charlson Co-morbidities Index (CCI). Subjects were divided into three groups, according to their BMI: individuals with BMI ≥30 kg/m2 (Group 1 n = 109, mean age 61 ± 1; 74.3% men), individuals with BMI ranging from 25.0 to 29.9 kg/m2 defined as overweight subjects (Group 2 n = 57, mean age 58.8 ± 1.4; 77% men), and subjects with a BMI ranging from 18.5 to 24.9 kg/m2 defined as normal weight subjects (Group 3 n = 19, mean age 54.2 ± 2.3; 64,2% men). RESULTS: In the whole population, the percentage cardiovascular risk was weakly related with BMI (r = 0.33; P < .001), but not with AHI. The cardiovascular risk was strictly related to the obesity (P < .00002), while the Epworth Questionnaire score and the Charlson Co-morbidity Index were respectively statistically higher in the group of obese individuals (P = .004, P = .0002) than in the other two sub-groups. When AHI values were stratified in tertiles, the percentage cardiovascular risk did not vary with increasing AHI values (Figure 2). CONCLUSIONS: Further studies are required to investigate the pivotal role of inflammation resulting from obesity, and underlying increased cardiovascular risk in OSA patients.

Breathing Rhythm Variations during Wash-In Do Not Influence Exhaled Volatile Organic Compound Profile Analyzed by an Electronic Nose.

E-noses are innovative tools used for exhaled volatile organic compound (VOC) analysis, which have shown their potential in several diseases. Before obtaining a full validation of these instruments in clinical settings, a number of methodological issues still have to be established. We aimed to assess whether variations in breathing rhythm during wash-in with VOC-filtered air before exhaled air collection reflect changes in the exhaled VOC profile when analyzed by an e-nose (Cyranose 320). We enrolled 20 normal subjects and randomly collected their exhaled breath at three different breathing rhythms during wash-in: (a) normal rhythm (respiratory rate (RR) between 12 and 18/min), (b) fast rhythm (RR > 25/min) and (c) slow rhythm (RR < 10/min). Exhaled breath was collected by a previously validated method (Dragonieri et al., J. Bras. Pneumol. 2016) and analyzed by the e-nose. Using principal component analysis (PCA), no significant variations in the exhaled VOC profile were shown among the three breathing rhythms. Subsequent linear discriminant analysis (LDA) confirmed the above findings, with a cross-validated accuracy of 45% (p = ns). We concluded that the exhaled VOC profile, analyzed by an e-nose, is not influenced by variations in breathing rhythm during wash-in.

Covid-19 and ex-smokers: an underestimated prognostic factor?

Dear Editor, The recent and explosive worldwide outbreak of Covid-19 leads many scientists and clinicians to identify the most responsible triggering risk factors in individuals without comorbidities, as well as potential prognostic factors. A notable field of research has been conducted on the role of smoking, which has been initially hypothesized as being a protective factor for Covid-19....

Obstructive Sleep Apnea: A View from the Back Door.

Obstructive sleep apnea (OSA) is a common disease that may affect up to 50% of the adult population and whose incidence continues to rise, as well as its health and socio-economic burden. OSA is a well-known risk factor for motor vehicles accidents and decline in work performance and it is frequently accompanied by cardiovascular diseases. The aim of this Special Issue is to focus on the characteristics of OSA in special populations which are less frequently investigated. In this regard, seven groups of experts in the field of sleep medicine gave their contribution in the realization of noteworthy manuscripts which will support all physicians in improving their understanding of OSA with the latest knowledge about its epidemiology, pathophysiology and comorbidities in special populations, which will serve as a basis for future research.

Exhaled breath profiling by electronic nose enabled discrimination of allergic rhinitis and extrinsic asthma.

AIM: To assess whether an e-nose could discriminate between subjects affected by allergic rhinitis with and without concomitant extrinsic asthma, as well as from healthy controls, in terms of exhaled VOC-profile. METHODS: Fourteen patients with Extrinsic Asthma and Allergic Rhinitis (AAR), 14 patients with Allergic Rhinitis without asthma (AR) and 14 healthy controls (HC) participated in a cross-sectional study. Exhaled breath was collected by a standardized method and sampled by an e-nose (Cyranose 320). Raw data were reduced by Principal component analysis and analyzed by canonical discriminant analysis. Cross-validation accuracy (CVA) and Receiver Operating Characteristic(ROC)-curves were calculated. External validation in newly recruited patients (7 AAR, 7 AR and 7 HC) was tested using the previous training model. RESULTS: Breathprints of patients with AR clustered from those with AAR (CVA = 85.7%), as well as HC (CVA = 82.1%). Breathprints from AAR were also separated from those of HC (CVA = 75.0%). External validation confirmed the above findings. CONCLUSIONS: An e-nose can discriminate exhaled breath from subjects with allergic rhinitis with and without extrinsic asthma, which represent two different diseases with partly overlapping features. This supports the view of using breath profiling to diagnose asthma also in patients with allergic rhinitis.

Electronic Nose Technology in Respiratory Diseases.

Electronic noses (e-noses) are based on arrays of different sensor types that respond to specific features of an odorant molecule, mostly volatile organic compounds (VOCs). Differently from gas chromatography and mass spectrometry, e-noses can distinguish VOCs spectrum by pattern recognition. E-nose technology has successfully been used in commercial applications, including military, environmental, and food industry. Human-exhaled breath contains a mixture of over 3000 VOCs, which offers the postulate that e-nose technology can have medical applications. Based on the above hypothesis, an increasing number of studies have shown that breath profiling by e-nose could play a role in the diagnosis and/or screening of various respiratory and systemic diseases. The aim of the present study was to review the principal literature on the application of e-nose technology in respiratory diseases.

The Prognostic Role of Obstructive Sleep Apnea at the Onset of Amyotrophic Lateral Sclerosis.

BACKGROUND/OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of central and peripheral motor neurons. Some studies have found discordant data in the presence of sleep apnea in ALS patients. An obstructive component also occurs with upper airways hypotonia and muscle weakness that may result in an excessive reduction of airway lumen, leading to obstructive sleep apnea (OSA). The aim of this study was to assess the role of obstructive apneic events at disease onset in the ALS prognosis. METHODS: A longitudinal retrospective study was conducted on 42 clinically diagnosed ALS patients. The study population was divided into 2 groups according to their obstructive apnea/hypopnea index (AHIo): group 1 consisted of 20 patients with an AHIo ≥5 and group 2 consisted of 22 patients with an AHIo <5. Both groups were compared with regard to demographic, polygraphic, and respiratory function parameters as well as ALS characteristics (bulbar onset, time between onset and first check-up, time between diagnosis and first check-up, time between first check-up and death or tracheostomy). RESULTS: The mean survival in ALS patients with an AHIo ≥5 was significantly shorter than in ALS without OSA (p = 0.0237). The sniff nasal inspiratory pressure test was significantly correlated with AHIo, time of oxyhemoglobin saturation below 90% and the oxyhemoglobin desaturation index (p < 0.0001). CONCLUSIONS: Our study highlights the importance of an early diagnosis of OSA in ALS patients, allowing the identification of ALS patients with an OSA phenotype (AHIo ≥5), who are characterized by a worse prognosis.

Evaluation of endothelial function and cardiovascular risk in non-obese patients with slight degree of obstructive sleep apnea syndrome.

Recently, it has been clearly described an independent relationship between obstructive sleep apnea syndrome (OSAS) and cardiovascular risk, with underlying mechanisms also including endothelial dysfunction. We enrolled 32 consecutive non-obese patients (mean age of 39.5±11.5 years), of which 16 with mild OSAS and 16 snoring without OSAS. Mild OSAS is defined by an AHI index between 5 and 15. We have investigated if whether there was a relationship between mild OSAS, endothelial function and carotid intima-media thickness (C-IMT). The population was divided into two groups: Group 1 (16 simple snorer patients with an average age of 39.4±12.1 years) and Group 2 (16 subjects with mild OSAS with an average age of 39.6±11.2 years). Each group underwent cardiovascular investigation including measurement of flow-mediated dilation (FMD) of the brachial artery and C-IMT. Both groups comprised non-obese subjects. Patients with mild OSAS had serum total cholesterol values statistically significantly higher than simple snores patients (178.6±24.9 vs 159.2±25.3; p=0.038). OSAS patients had also a trend towards higher values of maximum C-IMT compared to simple snorer patients (0.70±0.15 vs 0.65±0.16), although below the level of significance. Between the two groups, no difference was found for FMD values. The present results on mild OSAS strengthen the importance of a diagnosis of OSAS as soon as possible, in order to encourage all primary prevention interventions to correct risk factors responsible for disease progression and the occurrence of cardiovascular diseases, not excluding the use of therapies of non-invasive ventilation even in the early stages of the disease.

Echocardiographic findings and plasma endothelin-1 levels in obese patients with and without obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) and obesity are increasingly prevalent worldwide. Both promote endothelial dysfunction contributing to systemic and pulmonary hypertension over time. Endothelin-1 (ET-1) plays a pivotal role in the development of pulmonary hypertension (PH). The aim of the present study was to assess the association between plasma ET-1 and echocardiographic findings in obese individuals with and without OSA, as well as in non-obese patients with OSA. METHODS: Ninety-seven subjects (56 males) were enrolled in the study. All subjects underwent the following tests: venous endothelin-1 levels, pulmonary function testing, and arterial blood gas analysis. All patients except controls underwent transthoracic echocardiography and portable testing for sleep-disordered breathing. RESULTS: Plasma ET-1 levels were significantly higher in obese patients, both with and without OSA (respectively, n = 30 (mean value, 268.06 ± 49.56 pg/ml) and n = 32 (mean value, 263.12 ± 65.26 pg/ml)), compared with non-obese patients with OSA or to healthy controls (respectively, n = 20 (mean value, 149.8 ± 23.09 pg/ml) and n = 15 (mean value, 152.3 ± 27.64 pg/ml); p < 0.0001). Pulmonary artery pressure (PAPs) in obese patients with OSA were significantly higher than in obese patients without OSA (p < 0.0001), while there was no statistical difference between PAPs of obese patients without OSA, compared with the group of non-obese OSA patients. Plasma ET-1 levels significantly correlated with systolic PAPs in obese patients both with and without OSA (respectively, n = 30, r = 0.385, p = 0.03567; n = 32, r = 0.3497, p = 0.0497). CONCLUSIONS: Our study suggests that endothelin levels are more strongly associated with weight than the presence of sleep-disordered breathing, but pulmonary artery hypertension is associated with both weight and OSA.

Atrial flutter regression in HIV-associated pulmonary arterial hypertension after treatment with bosentan.

Pulmonary arterial hypertension (PAH) is a rare condition characterized by an increase in pulmonary arterial resistance leading to right heart failure and death. Arrhythmias are a growing problem in PAH; therefore, maintenance of sinus rhythm is considered to be an important treatment aim in these patients. We described the case of a 46-year-old woman with HIV-associated pulmonary arterial hypertension  who developed atrial flutter. After treatment with bosentan, it was observed a significant improvement in clinical and haemodynamic parameters. In addition, the AFL, which had previously persisted to both antiarrhythmic drug therapy and electrical stimulation, and had recurred after transthoracic electrical cardioversion, disappeared  in absence of any antiarrhythmic drug. Though the precise factors responsible for supraventricular arrhythmogenesis are still largely obscure, it is likely that initiation and maintenance of AFL may depend on all the conditions that can lead to increase in right atrial pressure, size, and wall stress, such as PAH. In our case, bosentan reduced both mean pulmonary artery pressure (mPAP) value and right heart chambers pressures. Therefore, it is conceivable that with the anatomical substrate needed for the maintenance of AFL being disappeared, sinus rhythm was restored.

Occupational asthma in a fruit and vegetables vendor.

BACKGROUND: This study presents a case report of a woman running a fruit and vegetables market stall, occupationally exposed to mushroom spores, who developed asthmatic symptoms. Basidiospores are allergens that can give rise to sensitization and subsequently trigger an allergic reaction, such as contact dermatitis, rhino-conjunctivitis, asthma and hypersensitivity pneumonitis. METHODS: A 40-year-old atopic woman, who had worked at a market stall selling fruit and vegetables for the past 26 years in a small town market in southern Italy, came to our attention at the Occupational Medicine Unit, complaining of a 3-year history of dyspnoea, cough, and wheezing during autumn and winter. RESULTS: Spirometry showed a severe mixed type respiratory deficit with a significant bronchodilator response obtained with salbutamol administration. Skin prick tests to common aeroallergens were negative. Prick-to-prick test with fresh Pleurotus ostreatus was positive. We evaluated the size of the skin wheals and compared them to the positive control according to the Skin Index. An on-the-spot inspection of her store was performed and environmental conditions were identified that did not allow a satisfactory air exchange. CONCLUSIONS: The clinical history and the results of the allergologic investigations, plus an on-the-spot inspection, permitted us to ascertain that this subject had developed occupational asthma due to Pleurotus ostreatus spores. We advised her to stop handling and selling mushrooms, and she has no longer suffered asthmatic symptoms, over seven years of follow-up, and regularly continued to work without needing to take anti-asthma drugs.