montelukast and Syndrome

One-third of pregnant asthmatics experience a worsening of their asthma that may progress to a critical asthma syndrome (CAS) that includes status asthmaticus (SA) and near-fatal asthma (NFA). Patients with severe asthma before pregnancy may experience more exacerbations, especially during late pregnancy. Prevention of the CAS includes excellent asthma control involving targeted early and regular medical care of the pregnant asthmatic, together with medication compliance. Spontaneous abortion risk is higher in pregnant women with uncontrolled asthma than in non-asthmatics. Should CAS occur during pregnancy, aggressive bronchodilator therapy, montelukast, and systemic corticosteroids can be used in the context of respiratory monitoring, preferably in an Intensive Care Unit (ICU). Systemic epinephrine should be avoided due to potential teratogenic side-effects and placental/uterine vasoconstriction. Non-invasive ventilation has been used in some cases. Intratracheal intubation can be hazardous and rapid-sequence intubation by an experienced physician is recommended. Mechanical ventilation parameters are adjusted based on changes to respiratory mechanics in the pregnant patient. An inhaled helium-oxygen gas admixture may promote laminar airflow and improve gas exchange. Permissive hypercapnea is controversial, but may be unavoidable. Sedation with propofol which itself has bronchodilating properties is preferred to benzodiazepines. Case reports delineating good outcomes for both mother and fetus despite intubation for SA suggest that multidisciplinary ICU care of the pregnant asthmatic with critical asthma are feasible especially if hypoxemia is avoided.

Topics: Abortion, Spontaneous; Acetates; Adrenal Cortex Hormones; Animals; Asthma; Bronchodilator Agents; Contraindications; Critical Illness; Cyclopropanes; Epinephrine; Female; Humans; Intensive Care Units; Medication Adherence; Pregnancy; Pregnancy Complications; Quinolines; Sulfides; Syndrome

The heterogeneity of asthma is illustrated by the significantly different features of pediatric asthma compared to adult asthma. One phenotype of severe asthma in pediatrics includes atopy, lack of reduction in lung function, and absence of gender bias as the main characteristics. Included in the NIH NAEPP EPR-3 are recommendations for the treatment and management of severe pediatric asthma and critical asthma syndrome, such as continuous nebulization treatments, intubation and mechanical ventilation, heliox, and magnesium sulfate. In addition, epinephrine, intravenous immunoglobulin, intravenous montelukast, extracorporeal membrane oxygenation, and many biological modulators currently under investigation are additional current and/or future treatment modalities for the severe pediatric asthmatic. But, perhaps the most important strategy for managing the severe asthmatic is preventative treatment, which can significantly decrease impairment and risk, particularly for severe acute exacerbations requiring emergency care and/or hospitalization. In order for preventative therapy to be successful, several challenges must be met, including selecting the correct therapy for each patient and then ensuring compliance or adherence to a treatment plan. The heterogeneity of asthma renders the former difficult in that not all patients will respond equally to the same treatment; the latter is only helpful if the correct treatment is employed. Strategies to ensure compliance include education of caregivers and patients and their families. As newer medications are introduced, options for individualized or customized medicine increase, and this may pave the way for significant decreases in morbidity and mortality in severe pediatric asthma.

Topics: Acetates; Animals; Asthma; Caregivers; Child; Critical Illness; Cyclopropanes; Humans; Hyperbaric Oxygenation; Immunoglobulins, Intravenous; Patient Compliance; Patient Education as Topic; Practice Guidelines as Topic; Quinolines; Respiration, Artificial; Sulfides; Syndrome

Bronchiolitis obliterans syndrome (BOS) is a severe manifestation of chronic graft-versus-host disease (cGVHD) following hematopoietic cell transplantation (HCT). Montelukast interrupts cysteinyl leukotriene (CysLT) activity and may diminish the activation and homing of cells to bronchioles and subsequent fibrosis. We performed a prospective phase II trial to test whether montelukast altered lung decline for patients with BOS after HCT. In this single-arm, open-label, multi-institutional study, the primary endpoints were stability or improvement (<15% decline) in forced expiratory volume in 1 second (FEV1) and a <1-point decline in the slope of FEV1 after 6 months of treatment. Secondary endpoints included symptom and functional responses and immune correlates investigating the role of leukotrienes in BOS progression. The study enrolled 25 patients with moderate to severe lung disease after 3 months of stable cGVHD therapy. Montelukast was well tolerated, and no patient required escalation of BOS-directed therapy. At the primary endpoint, all 23 evaluable patients met the criteria for treatment success using FEV1% predicted, and all but 1 patient had stable or improved FEV1 slope. In those with a >5% improvement in FEV1, clinically meaningful improvements were seen in the Lee scores of breathing, energy, and mood. Improvements in the Human Activity Profile and 6-minute-walk test were observed in those with a <5% decline in FEV1. Overall survival was 87% at 2 years. Immune correlates showed elevated leukotriene receptor levels on blood eosinophils and monocytes versus healthy controls, elevated urine leukotrienes in 45% of the cohort, and CysLT receptors in bronchoalveolar lavage subsets and a predominance of Th2 cells, all pretreatment. These data suggest that montelukast may safely halt the progression of BOS after HCT, and that leukotrienes may play a role in the biology of BOS.

Topics: Acetates; Bronchiolitis Obliterans; Cyclopropanes; Hematopoietic Stem Cell Transplantation; Humans; Prospective Studies; Quinolines; Sulfides; Syndrome

The aim of our study was to analyze the montelukast effectiveness in improving oculonasal symptoms, patient-reported outcomes (PROs), and eosinophilic biomarkers in patients with nonallergic rhinitis eosinophilic syndrome (NARES).. We enrolled prospectively 80 symptomatic patients treated with 10 mg once a day of montelukast in monotherapy for 2 months. All patients were investigated before and after treatment. Nasal symptoms (nasal obstruction, rhinorrhoea, sneezing, nasal itching), ocular symptoms (redness/puffiness, watery eyes), and other PROs (olfactory dysfunction, difficulty going to sleep, nighttime awakenings, and nasal congestion on awakening) were scored by visual analogic scale. The following clinical scores were assessed: Total Nasal Symptom Score (T4NSS), Total Ocular Symptom Score (T2OSS), Total Symptom Score of Patient-Reported Outcomes (TSS-PROs), and a Composite Symptoms Score (CSS). Patients were classified as responders when a reduction of at least 50% of the CSS was observed. Before and after treatment, the eosinophilic biomarkers in nasal lavage were analyzed: nasal eosinophilia (number of eosinophils per high power field), eotaxin-1 and eotaxin-2.. After treatment, significant reductions were observed for all the symptom scores. Forty-two of 78 patients were considered responders. A significant reduction of eosinophils in nasal mucosa and of levels of eotaxin-1 and eotaxin-2 in nasal lavage were observed after treatment in responder patients. Patients with asthma had an increased probability to be responders.. NARES patients may benefit from treatment with montelukast. In particular, the presence of concomitant asthma may be predictive of a greater efficacy.. 2 Laryngoscope, 129:551-557, 2019.

Topics: Acetates; Adult; Asthma; Biomarkers; Cyclopropanes; Eosinophilia; Eye Diseases; Female; Humans; Leukotriene Antagonists; Male; Nose Diseases; Prospective Studies; Quinolines; Rhinitis; Sulfides; Syndrome

Topics: Acetates; Aged; Anti-Bacterial Agents; Cyclopropanes; Drug Eruptions; Endocarditis, Bacterial; Eosinophilia; Humans; Immunoglobulins, Intravenous; Male; Methylprednisolone; Quinolines; Sulfides; Syndrome; Treatment Outcome; Vancomycin

Topics: Acetates; Antiretroviral Therapy, Highly Active; Cyclopropanes; HIV Infections; Humans; Immune System Diseases; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Sulfides; Syndrome

There is a high incidence of post-surgical recurrences of nasal polyps (NP) in patients suffering from the ASA Syndrome. The numerous theories as to the pathogenesis of the ASA Syndrome include an increase in lipoxygenase-mediated arachidonic acid metabolism, with the subsequent hyperproduction of leukotrienes (LT), and an inhibition of the cycloxygenase. Therefore, based on the information acquired on the immunobiological action mechanism of montelukast, a cysteinyl-LT receptor antagonist, it appeared worth testing the effectiveness of this substance in preventing post-surgical NP recurrences in a group of ASA Syndrome patients. After taking a case history, filling out a questionnaire scoring nasal symptoms, undergoing rhinoendoscopy and rhinomanometry, 40 patients suffering from ASA-Syndrome and NP (age range 30-72 years) were recruited for the study. They were uniformly classified according to Lund and Mackay using high resolution CT of the nose and paranasal sinuses performed after at least 1 month of nasal medical treatment. All the patients underwent microendoscopic anterior-posterior ethmoidectomy and bilateral maxillary antrostomy. After removing the nasal packing, the only treatment administered was 10 mg of montelukast/die for 6 months, with the drug suspended for 1 months after the first 3 months of treatment. The monthly follow-up included rhinoendoscopy, rhinomanometry and the questionnaire to score symptoms. After the seventh month a new CT was performed and compared with the pre-operative CT. In a control group of subjects, homogeneous with the test group, momethasone furoate nasal spray was administered at a dose of 100 mcg per nostril/die and loratadin tablets 10 mg/die. The results obtained in the patients treated with montelukast were analogous with those obtained in the second group, and during follow-up all patients showed total absence of any local recurrence, good nasal patency and no significant nasal symptom score on the questionnaire. In no case did the comparative CT, performed after the seventh month, show any signs of recurrence. The patients taking the montelukast reported a significant reduction in the use of steroids and bronchodilator inhalants during the course of the study than did the second group; indeed the number of asthmatic episodes dropped and they reported an improvement in the quality of life. Based on these results, the authors suggest that the use of montelukast in the treatment of post-surgical NP recurrences

Topics: Acetates; Adult; Aged; Aspirin; Asthma; Cyclopropanes; Drug Hypersensitivity; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Neoplasm Recurrence, Local; Quinolines; Sulfides; Syndrome