Search Results (57)

Background: Eosinophilic esophagitis (EoE) is a chronic type 2 immune-mediated esophageal disease defined by esophageal dysfunction and eosinophil-predominant inflammation. Beyond classic gastrointestinal symptoms, patients may present with aerodigestive complaints such as chronic cough, hoarseness, recurrent croup, stridor, vocal fold abnormalities, and subglottic stenosis, creating diagnostic overlap with laryngopharyngeal reflux, vocal fold dysfunction, asthma, allergic rhinitis, and other airway disorders. Methods: This scoping review mapped evidence on the relationship between EoE and laryngeal manifestations. PubMed/MEDLINE was searched using terms related to EoE, laryngeal disease, reflux, vocal fold pathology, and subglottic stenosis. Human English-language case reports, case series, observational studies, clinical trials, and reviews were narratively charted by study design, population, diagnostic criteria, laryngeal findings, reflux evaluation, treatment, and outcomes. Results: Laryngeal involvement in EoE appears clinically relevant but remains incompletely characterized. Direct eosinophilic infiltration of laryngeal or hypopharyngeal tissue is rare, whereas indirect mechanisms—including shared type 2 inflammation, epithelial barrier dysfunction, eosinophil and mast-cell mediators, reflux or microaspiration, and comorbid atopic airway disease—may contribute to symptoms and lesions. Pediatric patients may be especially likely to show airway-predominant presentations, including recurrent croup, chronic cough, and subglottic stenosis. Evidence is limited by heterogeneous definitions, inconsistent laryngoscopy or biopsy, variable reflux testing, and small observational reports. Conclusions: EoE should be considered in persistent or recurrent laryngeal symptoms, particularly when refractory to reflux or airway-directed therapy or associated with atopy. Multidisciplinary evaluation may improve recognition and management. Future studies should use standardized laryngeal assessment, pediatric case–control designs, and biomarker approaches linking EoE activity with objective laryngeal findings. Full article

We report the case of a 30-year-old female, non-smoker, with no known allergies or occupational exposures, presenting with a two-year history of recurrent stridor and wheezing, recently exacerbating over the past two months. Physical examination and routine laboratory tests were largely unremarkable. Pulmonary function tests were within normal limits, with no significant bronchodilator response. Chest CT revealed a 15 × 13 mm perihilar right-sided lesion adjacent to the right pulmonary artery. Bronchoscopy identified a nearly obstructive, highly vascularized endobronchial lesion at the origin of the right lower lobe bronchus, with involvement of the carina between the right middle and lower lobe bronchi. Histopathology confirmed a typical bronchial carcinoid. The patient underwent open right middle and lower lobe bilobectomy. What renders this case unusual is the combination of a prolonged two-year diagnostic delay with initial misdiagnosis as asthma, the critical anatomical location of the tumor at the bronchus intermedius with early involvement of the right middle lobe carina, and the consequent necessity of bilobectomy despite an otherwise low-risk, typical carcinoid histology. This case underscores the importance of considering endobronchial neoplasms in young, non-smoking patients with refractory or atypical airway symptoms, and highlights the role of integrated imaging and bronchoscopic evaluation in guiding individualized surgical planning. Full article

Background and Clinical Significance: Alpha-1 antitrypsin deficiency (AATD) is an autosomal codominant disorder caused by pathogenic variants in the SERPINA1 gene, resulting in reduced circulating alpha-1 antitrypsin (AAT) or production of dysfunctional protein. AAT is the principal inhibitor of neutrophil elastase, and its deficiency leads to unchecked proteolytic activity, progressive destruction of lung parenchyma, and increased susceptibility to infections. Severe deficiency, particularly in individuals homozygous for the Z allele (PI*ZZ), predisposes to early-onset panacinar emphysema, chronic airflow obstruction, and liver disease. Despite its clinical relevance, AATD remains markedly underdiagnosed and is frequently misclassified as smoking-related chronic obstructive pulmonary disease (COPD), delaying access to disease-modifying therapy, genetic counselling, and preventive strategies. Early recognition is therefore essential to improve outcomes. Case Presentation: We report the case of a 68-year-old ex-smoker with a long-standing diagnosis of “COPD” who presented with acute-on-chronic type 2 respiratory failure and community-acquired pneumonia. Spirometry revealed severe airflow obstruction, and high-resolution computed tomography demonstrated extensive basilar panlobular emphysema, raising suspicion for AATD. Serum AAT concentration was critically low at 26.8 mg·dL⁻¹, and isoelectric focusing confirmed a PI*ZZ phenotype. Next-generation sequencing identified homozygosity for the SERPINA1 c.1096G>A (Z) variant, with no additional pathogenic alleles. Cascade family screening revealed multiple heterozygous PI*MZ relatives. Before augmentation therapy could be initiated, the patient developed severe Legionella pneumophila pneumonia with secondary bacterial superinfection, progressing to refractory septic shock and death. Conclusions: This case illustrates how AATD can masquerade as smoking-related COPD for years, leading to missed opportunities for timely intervention. It underscores the importance of testing all adults with COPD or refractory asthma at least once, regardless of age or smoking history. Early diagnosis enables initiation of augmentation therapy, targeted vaccination, lifestyle modification, and genetic counselling, ultimately improving prognosis and reducing preventable morbidity and mortality. Full article

Asthma is increasingly recognized as a heterogeneous syndrome where traditional management fails, particularly given spirometry’s limitations in assessing small airway dysfunction. This review synthesizes the transition from clinical phenotyping to deep molecular endotyping, establishing a framework for precision medicine. We highlight the insufficiency of absolute eosinophil counts, proposing eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) as superior activation metrics. Furthermore, we explore Type 2 drivers (IL-4/IL-13, periostin) and epithelial alarmins like TSLP. Beyond classical immunology, the text describes metabolic dysregulation, specifically asymmetric dimethylarginine (ADMA) in obese-asthma phenotypes where nitric oxide synthase uncoupling promotes oxidative stress. We also analyze YKL-40 and surfactant protein D (SP-D) as markers of remodeling and barrier permeability, alongside microRNAs—specifically miR-21—in corticosteroid resistance. We conclude that managing refractory asthma requires shifting from reactive symptom control to an integrated analysis of multi-omic biomarkers. Establishing this comprehensive molecular profile via specialized centers is fundamental for addressing current diagnostic limitations, selecting biological therapies, and modifying the disease trajectory through an endotype-driven strategy addressing inflammatory, metabolic, and structural pathologies. Full article

Background: Pediatric bronchoscopy and bronchoalveolar lavage (BAL) are valuable procedures, used by pediatric pulmonologists in a wide variety of clinical scenarios. Reports of indications for BAL include investigations of infectious processes, for unusual or poorly responsive pneumonia, and non-infections reasons, including interstitial lung disease and aspiration syndromes. BAL in pediatric asthma is occasionally done in severe and uncontrolled asthma, to rule out co-morbid conditions or to investigate asthma phenotypes. We report here the results of BAL in young children with global pre-BAL diagnoses, with comprehensive analysis of the BAL cellularity and culture results, and with a post hoc review by an allergist. The results of BAL in children with enigmatic pulmonary processes were compared to the expected BAL cellularity in normal children, obtained by an expanded historical mini review. Methods: The initial objective was to perform a mini review of the collective published data for normal/control children with BAL differential cell counts with the purpose of using the results to compare normals to the information obtained on the symptomatic children with BAL results from pulmonologists in our combined allergy–pulmonary division. The exploratory study group was children 0–6 years of age who underwent a BAL from 2000 to 2024 at an academic pulmonary-allergy division. The children had presumptive diagnoses requiring investigation, including the most common diagnoses of asthma, chronic cough, aspiration, or refractory bronchitis, and in this post hoc protocol only the diagnoses provided on the pre- and/or post-operative summary by the divisional pulmonologist(s) performing the BAL were used in the post hoc analysis. Secondarily, the operative day pre- and/or post-lavage diagnoses were used to divide the children into groups (based on operative day diagnoses) to stratify their lavage results, based on eosinophils, neutrophils, culture positivity and lipid-laden macrophages. Normative data collected from the literature was used as the historically expected results for the BAL group(s) analysis. Results: A mini review of BAL cellularity across 25+ years of literature was performed to establish normative data for our subsequent analysis. Both eosinophils and neutrophils are low or absent in normal children based on the comprehensive literature review. As a part of a larger cohort of 500 children ages 0–20 years, 317 children ages 0–6 were selected for review. The protocol was approved by the University Institutional Review Board. Using the mini review as reference, we found that eosinophil counts of one or more were recovered in over 20% of all children, regardless of bronchoscopy indication. Neutrophilia > 50% of cells and/or bacteria colony counts > 100,000 organisms were also frequent findings (>50 percent of the children). As a separate observation, lipid-laden macrophages did not isolate to aspiration indications for the bronchoscopy and lavage. Conclusions: An updated mini review of the cellularity expected in control children provided a context to the findings in our studied exploratory sample population. There was a high recovery of neutrophils coupled with culture positivity found across all children undergoing BAL. Eosinophils > 1 were present in up to 25% with a pre-lavage asthmatic symptom indication, but almost an equal percentage in other children with non-asthma-like conditions was surprising. Lipid-laden macrophage data was unhelpful. Full article

Background: Asthma exhibits marked heterogeneity both clinically and at the molecular phenotypic level, requiring specifically targeted treatments to block the key pathways of the disease. Monoclonal-antibody-based biologics targeted at critical inflammatory pathways of T2 inflammation such as IL-5, IL-5R, IL-4, and IL-13 are increasingly regarded as effective treatments for severe refractory eosinophilic asthma. Methods: This review provides an update on the potential of straightforward and reproducible biomarkers to aid in the selection of the biologic-based therapy most likely to be effective in patients with severe or refractory eosinophilic asthma based on English-language original articles in PubMed or MedLine. Results: Monoclonal-antibody-based biologic therapies have revolutionised severe asthma management, enabling reductions in symptoms that include exacerbations, discontinuation of oral corticosteroids, improved lung function, and enhanced quality of life. Significant clinical effects with anti-IL-5 or -IL-4/13 monoclonal antibodies are more likely to be seen when simple predictive biomarkers such as serum periostin, fractional exhaled nitric oxide (FENO), or blood eosinophil counts are used to aid in the identification of those patients with severe refractory eosinophilic asthma who are most likely to benefit from biologic therapies. Conclusions: Biologic-based therapy aimed at T2 inflammation benefits patients with severe eosinophilic asthma, particularly when guided by biomarkers that do not require direct sampling of the airways to target therapy, who are most likely to benefit from these treatments, with good safety profiles for these therapies. Full article

Background and Clinical Significance: Otitis media with effusion (OME) is characterized by persistent middle ear effusion without acute infection. Type 2 inflammation, mediated by IL-4 and IL-13 signaling via the IL-4Rα receptor, has been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and possibly OME. Refractory OME in adults remains a therapeutic challenge, as conventional treatments often fail to achieve long-term resolution. Targeted biologic therapies that modulate type 2 inflammation may offer a novel treatment option. Case Presentation: We report the case of a 60-year-old man with a 15-year history of allergic rhinitis and CRSwNP, complicated by recurrent asthma exacerbations, who presented with bilateral aural fullness, hearing loss, and tinnitus. His symptoms persisted despite repeated tympanic punctures, Eustachian tube insufflation, and corticosteroid therapy. Otoscopy revealed dull tympanic membranes with effusion, and audiometry showed conductive hearing loss with a B-type tympanogram on the left. Laboratory findings demonstrated mild peripheral eosinophilia. The patient was diagnosed with OME, likely secondary to type 2 inflammation. After nine biweekly injections of Stapokibart (CM310)—a humanized monoclonal antibody targeting IL-4Rα—aural fullness completely resolved. Otoscopic findings and tympanograms normalized, and hearing thresholds improved significantly. Retrospective evaluation using Iino’s diagnostic framework suggested that the patient did not meet the full criteria for eosinophilic otitis media (EOM); nevertheless, marked symptomatic and functional improvement was achieved. No recurrence or adverse effects were observed during follow-up. Conclusions: This case suggests that IL-4Rα blockade with Stapokibart may be effective in treating refractory OME associated with type 2 inflammation, even in patients who do not fulfill the diagnostic criteria for EOM. These findings highlight the potential of anti-IL-4Rα biologics as a novel therapeutic option for middle ear diseases driven by type 2 inflammation. Full article

Background/Objectives: Asthma exacerbations are among the most frequent causes of pediatric emergency department (ED) visits, with over 700,000 annual cases in the United States and a significant number in Europe. Children under five years of age are particularly vulnerable to hospitalization. Methods: As timely assessment of exacerbation severity in the ED is critical, this review synthetizes data about tools such as the Pediatric Respiratory Assessment Measure (PRAM) and the Asthma Severity Score (ASS) aid in evaluating clinical status based on respiratory rate, oxygen saturation, accessory muscle use, and response to treatment. We also analyzed the proper management following established guidelines from GINA, NAEPP and other articles. Results: First-line therapy includes oxygen supplementation, short-acting beta-agonists (SABAs) administered frequently during the first hour, and early systemic corticosteroids. In moderate to severe cases, ipratropium bromide is added. For refractory or life-threatening presentations, intravenous magnesium sulfate, epinephrine, or ventilatory support may be required. Discharge is appropriate when symptoms resolve, oxygen saturation remains >94% on room air, and the child demonstrates adequate inhaler use. Hospitalization is indicated in cases of persistent hypoxemia, poor response, feeding difficulties, or social concerns. Post-discharge care includes thorough caregiver education, medication access, and a personalized asthma action plan to reduce recurrence risk. Conclusions: The effective diagnosis, appropriate exacerbation treatment, monitoring of patients in the post-attack period, as well as successful preventive medication play a key role in the management of pediatric patients with asthma. Full article

Asthma is a chronic inflammatory disease with a heterogeneous course, often progressing silently from mild symptoms to severe, treatment-refractory disease. Current guidelines recommend biologic therapies after failure of high-dose inhaled corticosteroids and additional controllers, typically in patients with frequent exacerbations. This reactive approach may delay intervention until irreversible airway remodeling has occurred, limiting the potential benefits of biologic therapy. Therefore, severe asthma may be envisioned as the consequence of missed opportunities for early interventions. Early initiation of biologic therapy—guided by biomarkers such as blood eosinophil count and fractional exhaled nitric oxide (FeNO), as well as symptom burden and risk of lung function decline—may prevent progression to severe asthma and improve remission rates. This position paper advocates for a shift from severity-based to risk-based treatment strategies, recommending earlier biomarker assessment, redefinition of escalation criteria, and clinical trials designed to evaluate biologics in symptomatic non-exacerbating patients. By recognizing persistent inflammation and progression risk earlier in the disease course, clinicians may have a critical opportunity to alter the trajectory of asthma, reduce long-term morbidity, and achieve sustained control before irreversible damage occurs. Full article

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic upper airway disease that may involve different inflammatory endotypes, although in Western populations it is most commonly associated with type 2 inflammation. CRSwNP has a significant impact on the patient’s quality of life. The recommended appropriate medical therapy is effective in controlling CRSwNP symptoms in many patients; however, a subset continues to exhibit persistent type 2 inflammation, evidenced by recurrent nasal polyps, elevated eosinophil counts, or the need for systemic corticosteroids or surgery. Monoclonal antibodies have recently become a novel and personalized treatment that can help refractory patients restore disease control. Objective: The present study aims to evaluate the effectiveness of mepolizumab in real-world settings in a diverse patient population, focusing on assessing the impact of this therapy on patient-reported outcomes after six months of treatment. Methods: This is a multicenter, observational study of CRSwNP patients treated with mepolizumab carried out in five hospitals located in Spain. Adult patients with a diagnosis of uncontrolled CRSwNP were included in the study. The change in the nasal polyp score (NPS) was the main clinical endpoint. Changes in the Sinonasal Outcome Test (SNOT-22), nasal congestion and smell impairment visual analogue scale scores, and blood and nasal polyp tissue eosinophil counts were among other endpoints included. Results: In total, 47 patients were included, and 91% were asthmatic. The nasal polyp score (0–8) was reduced significantly in the cohort (mean change: −2.56, p < 0.0001). The mean SNOT-22 score improved 25.29 points. Nasal congestion (−3.57, p < 0.0001) and smell impairment (−4.0, p < 0.0001) visual analog scale scores (0–10) showed a significant improvement. Blood and tissue eosinophil median counts showed significant reductions versus baseline of 86% and 26%, respectively. Among those patients with asthma, the asthma control test score achieved a median value of 24 points. Conclusions: This study provides real-world evidence supporting the effectiveness of mepolizumab in managing CRSwNP in patients with features suggestive of type 2 inflammation. The observed improvements in patient-reported outcomes, nasal polyp burden, and asthma control suggest that mepolizumab may be a valuable therapeutic option for this patient population. Full article

Topical percutaneous drug delivery has recently emerged as a novel strategy for the treatment of allergic diseases, offering targeted drug delivery to mucosal tissues adjacent to the skin. Unlike conventional topical approaches that act on the skin surface or mucosal membranes, topical percutaneous drug delivery enables non-invasive pharmacologic modulation of deeper structures such as the conjunctiva, nasal mucosa, and trachea. This review explores the rationale, pharmacokinetic foundation, clinical data, and future prospects of transdermal therapy in allergic conjunctivitis, allergic rhinitis, and asthma-related cough. In allergic conjunctivitis, eyelid-based transdermal delivery of antihistamines such as diphenhydramine and epinastine has shown rapid and long-lasting symptom relief, with epinastine cream recently approved in Japan following a randomized controlled trial (RCT) demonstrating its efficacy. Preclinical and clinical pharmacokinetic studies support the eyelid’s unique permeability and sustained drug release profile, reinforcing its utility as a delivery site for ocular therapies. In allergic rhinitis, diphenhydramine application to the nasal ala demonstrated symptomatic improvement in patients intolerant to intranasal therapies, though anatomical separation from the inflamed turbinates may limit consistent efficacy. Similarly, cervical tracheal application of steroids and antihistamines has shown potential benefit in asthma-related cough, especially for patients refractory to inhaled treatments, despite anatomical and depth-related limitations. Overall, site-specific anatomy, skin permeability, and disease localization are critical factors in determining therapeutic outcomes. While trans-eyelid therapy is supported by robust data, studies on the nasal ala and trachea remain limited to small-scale pilot trials. No major adverse events have been reported with nasal or tracheal application, but eyelid sensitivity requires formulation caution. To validate this promising modality, further RCTs, pharmacokinetic analyses, and formulation optimization are warranted. Topical percutaneous drug delivery holds potential as a non-invasive, site-directed alternative for managing allergic diseases beyond dermatologic indications. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a subtype of chronic rhinosinusitis (CRS) characterized by bilateral nasal polyps, primarily affecting adults. It is often associated with hyposmia and asthma and driven by persistent Th2 inflammation, particularly in Caucasian patients. The disease is recurrent and significantly impacts quality of life, yet its pathophysiology remains poorly understood. Management includes intranasal steroids, short courses of systemic corticosteroids, surgery for refractory cases, and biologics. However, despite these treatment options, disease control remains challenging. Low vitamin D levels have been associated with worse clinical outcomes, while supplementation studies show promise in improving symptoms in deficient patients. Emerging research suggests that vitamin D modulates immunity, fibroblast activity, and epithelial integrity, potentially contributing to CRSwNP pathogenesis, though the exact mechanisms remain unclear. This review synthesizes current research on vitamin D’s role in systemic and local inflammation in CRSwNP. By highlighting its potential therapeutic implications, this work aims to guide future research and inform clinical practice. Additionally, it may serve as a foundation for understanding the broader impact of vitamin D deficiency in sinonasal diseases and other atopic conditions. Full article

The beneficial effects of cannabinoids in the treatment of respiratory diseases have been drawing researchers’ attention for several decades. Asthma is a complex disease entity characterized by a variable course, the treatment of which requires the continuous search for alternative, adjuvant treatment strategies designed for patients refractory to available pharmacotherapies. Cannabinoids exert certain physiological responses in the respiratory system due to their immunomodulatory properties and the strong presence of the endocannabinoid system in the lungs. In animal model studies, THC and CBD seem to counteract bronchoconstriction and inhibit pro-inflammatory mediation, respectively, which highlights their possible future contribution to the treatment of respiratory and allergic diseases, such as asthma. However, there are controversies regarding the health consequences of cannabis usage, the extracts’ proportions, or equally safe and effective routes of administration, especially considering the alarming reports indicating an increased risk of asthma development among recreational cannabis smokers. The purpose of this review is to analyze the available literature on the influence of the endocannabinoid system, phytocannabinoids, and their modes of action on asthma pathogenesis in an attempt to assess their potential clinical relevance and determine future research directions. Full article

Microbial, especially fungal, sensitization has been associated with the development and exacerbation of treatment-refractory neutrophilic asthma. Among the airway-inhabiting fungi, Aspergillus fumigatus and Candida albicans are the dominant species that elicit protective T helper (Th) 17 and other T cell responses, contributing to airway neutrophilia and steroid resistance. However, it is not fully understood how fungal airway colonization impacts the immunopathogenesis of asthma. Here, we used a neutrophilic asthma model induced by C. albicans to study the immune regulation of this disease. We found that intranasal administration of C. albicans induced platelet infiltration into the lung. Platelet-expressed latent TGF-β could be activated specifically by Th17 cells and drive the commitment, maintenance, and expansion of Th17 cells. In Candida-induced asthma, an adoptive transfer of platelets enhanced Th17 responses, increasing airway neutrophil influx. Thus, managing airway mycobiota and reducing platelet intrapulmonary infiltration may serve as a promising interventional approach. Full article

In severe asthma, symptoms are unstable despite intensive treatment based on high doses of inhaled corticosteroids and on-demand use of oral corticosteroids. Although, recently, various biological agents related to Th2 cytokines have been added to intensive controller medications for severe asthma, a significant progress has not been observed in the management for symptoms (dyspnea, wheezing and cough). Medical treatment focused on Type 2 inflammation is probably insufficient to maintain good long-term management for severe asthma. Airway eosinophilia and decreased reversibility in forced expiratory volume in 1 second (FEV₁) are listed as major predictors for exacerbation-prone asthma. However, it is generally considered that asthma is complex and heterogeneous. It is necessary to establish precision medicine using treatable traits based on a multidimensional approach related to asthma. Since phospholipids generate lysophospholipids and arachidonic acid by phospholipases, lysophospholipids can be associated with the pathogenesis of this disease via action on smooth muscle, endothelium, and epithelium in the airways. Lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), and sphingosine 1-phosphate (S1P) are increased in bronchoalveolar fluid after allergen challenge. LPA, LPC, and S1P recruit eosinophils to the lungs and cause β₂-adrenergic desensitization. LAP and S1P cause contraction and hyperresponsiveness in airway smooth muscle. Moreover, lysophosphatidylserine and S1P are associated with the allergic reaction related to IgE/FcεRI in mast cells. Lysophospholipid action is probably comprised of corticosteroid resistance and is independent of Type 2 inflammation, and may be corelated with oxidative stress. Lysophospholipids may be a novel molecular target in advancing the management and treatment of asthma. This review discusses the clinical relevance of lysophospholipids in asthma. Full article