Management of Persistent SARS-CoV-2 Infection in Patients with Follicular Lymphoma.

INTRODUCTION: There is no consensus on the management of the coronavirus disease (COVID-19) in patients with secondary immunosuppression due to either an underlying hematological disease or to the effects of immunochemotherapy (ICT). Some of them may present persistent infection with multiple relapses of COVID-19, requiring several admissions. This study evaluated the clinical characteristics and outcomes after treatment of 5 patients with follicular lymphoma (FL), previously treated with ICT, who developed several episodes of COVID-19. METHODS: We analyzed the clinical evolution and response to treatment with antiviral agent, steroids, and convalescent plasma in 5 patients with FL and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persistent infection. Reverse transcriptase polymerase chain reaction tests and peripheral blood immunophenotype were performed for all patients. RESULTS: All patients required hospitalization due to pneumonia with severity criteria and were re-admitted after a median of 22 days (13-42) from the previous discharge. They all showed B-cell depletion by immunophenotyping, and no traces of immunoglobulin antibodies against SARS-CoV-2 were detected in any of the cases. The survival rate was 80%. CONCLUSION: The combination therapy evidenced clinical benefits, demonstrating its capacity to control infection in immunosuppressed FL patients treated with ICT.

Safety of biological therapy in elderly patients with severe asthma.

OBJECTIVE: To assess the safety of biological therapy for severe T2 asthma (omalizumab, mepolizumab, benralizumab and reslizumab) under real-life conditions in elderly patients older than 70 years. METHODS: Retrospective data collection including clinical characteristics, comorbidities, treatment, disease control and adverse events (AE) of all patients with severe asthma on biological therapy older than 70 years seen in the Severe Asthma Unit of our hospital. RESULTS: Of 147 patients with severe asthma being treated with biologics, 21 patients older than 70 years were included. The median age of these patients was 76.3 years (range 71-86) and the majority were women (n = 18, 85.7%). There were 9 patients (42.9%) who experienced an AE related to biological treatment. Four (44.4%) were in treatment with omalizumab, two (22.2%) with mepolizumab, two patients (22.2%) with reslizumab and one (11.1%) with benralizumab. The median FEV1 (%) was 66%. These patients had a considerably higher body mass index (BMI). No significant differences were found for any other variable. Most of the AE reported were considered mild with the exception of one case of systemic AE (anaphylaxis) associated with omalizumab. CONCLUSION: This study indicates that the prescription of biological therapy in elderly patients with severe asthma seems to be safe. More evidence is needed in this particular population.

A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia.

A high proportion of patients with acute myeloid leukemia who achieve minimal residual disease negative status ultimately relapse because a fraction of pathological clones remains undetected by standard methods. We designed and validated a high-throughput sequencing method for minimal residual disease assessment of cell clonotypes with mutations of NPM1, IDH1/2 and/or FLT3-single nucleotide variants. For clinical validation, 106 follow-up samples from 63 patients in complete remission were studied by sequencing, evaluating the level of mutations detected at diagnosis. The predictive value of minimal residual disease status by sequencing, multiparameter flow cytometry, or quantitative polymerase chain reaction analysis was determined by survival analysis. The sequencing method achieved a sensitivity of 10-4 for single nucleotide variants and 10-5 for insertions/deletions and could be used in acute myeloid leukemia patients who carry any mutation (86% in our diagnostic data set). Sequencing-determined minimal residual disease positive status was associated with lower disease-free survival (hazard ratio 3.4, P=0.005) and lower overall survival (hazard ratio 4.2, P<0.001). Multivariate analysis showed that minimal residual disease positive status determined by sequencing was an independent factor associated with risk of death (hazard ratio 4.54, P=0.005) and the only independent factor conferring risk of relapse (hazard ratio 3.76, P=0.012). This sequencing-based method simplifies and standardizes minimal residual disease evaluation, with high applicability in acute myeloid leukemia. It is also an improvement upon flow cytometry- and quantitative polymerase chain reaction-based prediction of outcomes of patients with acute myeloid leukemia and could be incorporated in clinical settings and clinical trials.

Asthma diagnosis using integrated analysis of eosinophil microRNAs.

BACKGROUND: Asthma is a syndrome characterized by airway inflammation and obstruction. Due to its heterogeneity, the difficulties in asthma diagnosis and treatment make the discovery of new biomarkers a focus of research. So, we determined the differential miRNA expression of eosinophils between healthy and asthmatic patients and to establish a differentially expressed miRNA profile detectable in sera for use as biomarker. METHODS: MicroRNAs from peripheral eosinophils from healthy and asthmatic subjects were isolated and analyzed by next-generation sequencing and confirmed by quantitative PCR in 29 asthmatics and 10 healthy individuals. The levels of serum miRNAs were performed by quantitative PCR in 138 asthmatics and 39 healthy subjects. Regression analysis and Random Forest models were performed. RESULTS: We found a set of miRNAs whose expression differs between eosinophils from asthmatics and healthy subjects. These miRNAs can classify asthmatics into two clusters that differed in the number of eosinophils and periostin concentration in serum. Some of these miRNAs were also confirmed in sera, as miR-185-5p which discriminates asthmatics from healthy subjects. Together with other two miRNAs, miR-185-5p allowed us to create a logistic regression model to discriminate better both conditions and a Random Forest model that can even sort the asthmatics into intermittent, mild persistent, moderate persistent, and severe persistent asthma. CONCLUSION: Our data show that miRNAs profile in eosinophils can be used as asthma diagnosis biomarker in serum and that this profile is able to rank asthma severity.

Relationship between upper airway diseases, exhaled nitric oxide, and bronchial hyperresponsiveness to methacholine.

OBJECTIVE: The "united airway disease" concept is based on the bidirectional interaction between asthma and rhinitis. The aim of this study was to determine the relationship between upper airway diseases and bronchial hyperresponsiveness (BHR), as well as their association with the fractional concentration of exhaled nitric oxide (FeNO) and atopy in patients with persistent symptoms suggestive of asthma requiring methacholine challenge testing (MCT) to confirm asthma diagnosis. METHODS: A cross-sectional prospective study was carried out in adult patients with persistent asthma-like symptoms and negative bronchodilator testing. FeNO and MCT were performed in all patients. Asthma was confirmed based on the presence of suggestive symptoms and MCT results. Associated upper airway diseases included allergic rhinitis, nonallergic rhinitis, chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD). RESULTS: The study included 575 patients; asthma was confirmed in 32.3%, and FeNO values ≥ 50 ppb were found in 27% of the patients. Elevated FeNO was significantly associated to AERD. The prevalence of atopy in asthma patients was 86.6%. Atopy was present in 90.4% of patients with asthma and FeNO levels ≥ 50 ppb. A significant association was found between AERD, asthma, and FeNO ≥ 50 ppb. CONCLUSIONS: Patients with symptoms suggestive of asthma but negative bronchodilator testing are commonly seen in usual practice. In this population, the association of high FeNO levels and BHR to atopy, as well as to AERD, suggests the presence eosinophilic inflammation in both the upper and lower airways and supports the "one airway" hypothesis.

Bronchiectasis in severe asthma: Clinical features and outcomes.

BACKGROUND: Bronchiectasis is increasingly being identified in patients with severe asthma and could contribute to disease severity. OBJECTIVE: To determine the prevalence of bronchiectasis in a population of patients with severe asthma and to better characterize the clinical features of these patients and their outcomes. METHODS: We retrospectively reviewed the medical files of 184 subjects with confirmed severe asthma who had undergone high-resolution thoracic computed tomography and compared the characteristics and outcomes of subjects with and without bronchiectasis. RESULTS: Bronchiectasis was identified in 86 patients (47%). These patients had concomitant hypersensitivity to nonsteroidal anti-inflammatory drugs (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.00-5.03) and gastroesophageal reflux disease (OR 1.89, 95% CI 1.05-3.41) more frequently than subjects without bronchiectasis, but had less atopic dermatitis (OR 0.188, 95% CI 0.04-0.88). Subjects with bronchiectasis were more frequently hospitalized for asthma exacerbations (OR 2.09, 95% CI 1.08-4.05) and had higher blood eosinophil levels (464 vs 338; P = .005) than subjects without bronchiectasis. CONCLUSION: Our study suggests that in subjects with severe asthma, the presence of bronchiectasis is associated with more frequent hospitalizations, concomitant gastroesophageal reflux disease, hypersensitivity to nonsteroidal anti-inflammatory drugs, and higher blood eosinophil counts. Bronchiectasis could represent an additional phenotypic feature of severe eosinophilic asthma.

Predictors of asthma relapse in patients who attended an emergency department.

BACKGROUND: Patients with asthma exacerbations and frequent relapses that require admission to the emergency department (ED) often have more severe disease, worse quality of life, and higher use of health care resources. OBJECTIVE: The aim of this study was to identify potential predictors of relapse after patients are treated in an ED for an asthma exacerbation. METHODS: A retrospective, noninterventional cohort study was conducted in adult patients who attended the ED of a tertiary hospital in 2014 for an asthma exacerbation. We analyzed the subpopulation who experienced at least one relapse (returned to the ED < 15 days after the previous event). RESULTS: Fifty-two of 831 patients experienced 66 relapses after going to the ED (mean ± standard deviation [SD] age, 58.5 ± 23.4 years). The average ± SD probability of a relapse was 6 ± 0.8%. The frequency of episodes was higher in May and November. Twenty-four patients had ≥260 blood eosinophils/µL, including 17 who had ≥400 eosinophils/µL. Only 15% of the patients were referred to an asthma specialist at discharge. Factors related to a higher probability of relapse were the following: having multiple visits to the ED in 1 year, uncontrolled asthma, wheezing in the pulmonary auscultation, peripheral eosinophilia with ≥400 eosinophils/ µL, and being discharged in the first visit to the ED (p < 0.01 for all). CONCLUSION: In this population, patients who had multiple ED visits in 1 year, those with uncontrolled asthma, wheezing, ≥400 blood eosinophils/µL, or who had been discharged at the first ED visit are at higher risk of relapse.

Presence of acute and chronic renal failure in patients with paroxysmal nocturnal hemoglobinuria: results of a retrospective analysis from the Spanish PNH Registry.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening blood disease. With the advent of eculizumab treatment, renal function has substantially improved, although no data from real-world clinical practice are available. An observational, retrospective, multicenter study was conducted in Spain on clinical data obtained from outpatient visits of patients with PNH (Spanish PNH Registry) who had experienced acute (ARF) or chronic (CRF) renal failure. Of the 128 patients registered (April 2014), 60 were diagnosed with classic PNH. Twenty-seven (45.0%) patients with a mean age of 48.5 (±16.2) years had renal failure, ARF or CRF, and were included in this study. Near half of the patients (n = 13; 48.1%) presented with ARF alone, 33.3% (n = 9) had CRF with episodes of ARF, while 18.5% (n = 5) were diagnosed with CRF alone. For patients with diagnosis of PNH and renal failure (n = 27), the median time to the first ARF episode was 6.5 (CI 95%; 2.2, 14.9) years, whereas the median to the diagnosis of CRF was 14.5 (CI 95%; 3.8, 19.2) years after the diagnosis of PNH. Patients with ARF (n = 22) were treated with eculizumab and did not experience new episodes of ARF, except for one patient with sepsis. Of the patients with CRF, two received treatment without experiencing further episodes of ARF. Sixteen patients who completed treatment (11 with ARF and 5 with ARF + CRF) recovered from the episode of ARF or from CRF. Of the remaining patients treated with eculizumab, one patient improved from stages III to II, three patients stabilized without showing disease progression, and one patient progressed from stages III to IV. Treatment with eculizumab in PNH patients has beneficial effects on renal function, preventing ARF and progression to CRF.

Biomarkers in Occupational Asthma.

PURPOSE OF REVIEW: Work-related asthma is a common disorder among adult asthma patients, and in the case of occupational asthma, it is induced by workplace exposures. RECENT FINDINGS: Occupational asthma provides an excellent model and benchmark for identifying and testing different allergy or inflammatory biomarkers associated with its inception or progression. Moreover, specific inhalation challenge with the incriminated agent represents an experimental setting to identify and validate potential systemic or local biomarkers. Some biomarkers are mainly blood-borne, while local airway biomarkers are derived from inflammatory or resident cells. Genetic and gene-environment interaction studies also provide an excellent framework to identify relevant profiles associated with the risk of developing these work-related conditions. Despite significant efforts to identify clinically relevant inflammatory and genomic markers for occupational asthma, apart from the documented utility of airway inflammatory biomarkers, it remains elusive to define specific markers or signatures clearly associated with different endpoints or outcomes in occupational asthma.

Cost-effectiveness of asthma therapy: a comprehensive review.

BACKGROUND: Asthma has an important impact in terms of both direct and indirect costs. In Europe, the disease costs € 19 000 million a year. Moreover, the cost is greater among patients with severe uncontrolled asthma and is even higher when the work productivity is also taken into account. Improved control of the disease results in cost savings. In this context, cost-effectiveness and cost-utility studies offer important information for clinicians in deciding the best treatment options for asthmatic patients and contribute to ensure an efficient use of the available healthcare resources. METHODS: An English and Spanish literature search using electronic search engines (PubMed and EMBASE) was conducted in peer-review journals, from 2009 to June 2014. In order to perform the search for the most suitable and representative articles, key words were selected ("asthma", "cost-effectiveness", "cost-utility", "QALY", "cost-benefit", "economic impact of asthma" "healthcare cost", "asthma treatment" and "work productivity with asthma"). RESULTS: Two-hundred forty-three titles and abstracts were identified by the primary literature search. The full text of the potentially 76 eligible papers was reviewed, and 22 articles were qualified to be finally included. CONCLUSIONS: This article provides a comprehensive review on the evidence of cost-effectiveness of asthma treatments derived from the published literature and offers an overall summary of the socioeconomic burden of asthma and its relationship with the degree of disease control. Management alternatives, such as the use of combination therapy with ICS/LABA or omalizumab, when administered according to their current therapeutic indications, have been shown to be cost-effective.

SOCS3 silencing attenuates eosinophil functions in asthma patients.

Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process.

Diagnostic Accuracy of Specific IgE Against Wheat and Rye in Flour-Induced Occupational Asthma.

BACKGROUND: Assessment of IgE-mediated sensitization to flour allergens is widely used to investigate flour-induced occupational asthma. The diagnostic efficiency of detecting specific IgE antibodies (sIgEs) against wheat and rye flour, however, has not been thoroughly compared with other diagnostic procedures. OBJECTIVE: We sought to evaluate the diagnostic accuracy of sIgE against wheat and rye compared with specific inhalation challenge (SIC) with flour as the reference standard. METHODS: This retrospective multicenter study included 264 subjects who completed an SIC with flour in eight tertiary centers, of whom 205 subjects showed a positive SIC result. RESULTS: Compared with SIC, sIgE levels of 0.35 kUA/L or greater against wheat and rye provided similar sensitivities (84% to 85%, respectively), specificities (71% to 78%), positive predictive values (91% to 93%), and negative predictive values (56% to 61%). Increasing the threshold sIgE value to 5.10 kUA/L for wheat and to 6.20 kUA/L for rye provided a specificity of 95% or greater and further enhanced the positive predictive value to 98%. Among subjects with a positive SIC, those who failed to demonstrate sIgE against wheat and rye (n = 26) had significantly lower total serum IgE level and blood and sputum eosinophil counts and a lesser increase in postchallenge FeNO compared with subjects with a detectable sIgE. CONCLUSION: High levels of sIgE against wheat and/or rye flour strongly support a diagnosis of flour-induced occupational asthma without the need to perform an SIC. The absence of detectable sIgE against wheat and rye in subjects with a positive SIC seems to be associated with lower levels of TH2 biomarkers.

COVID-19 Outcomes in Patients with Hematologic Malignancies in the Era of COVID-19 Vaccination and the Omicron Variant.

A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64-2.87), with >1 comorbidity (2.44, 1.85-3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19-2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2-0.37) or BA.4/BA.5 (0.13, 0.08-0.19) periods and among patients vaccinated with one or two (0.51, 0.34-0.75) or three or four (0.22, 0.16-0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03-3.25) and Omicron (3.19, 95% CI 1.59-6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients.

Identification of Asthma Phenotypes in the Spanish MEGA Cohort Study Using Cluster Analysis.

INTRODUCTION: The definition of asthma phenotypes has not been fully established, neither there are cluster studies showing homogeneous results to solidly establish clear phenotypes. The purpose of this study was to develop a classification algorithm based on unsupervised cluster analysis, identifying clusters that represent clinically relevant asthma phenotypes that may share asthma-related outcomes. METHODS: We performed a multicentre prospective cohort study, including adult patients with asthma (N=512) from the MEGA study (Mechanisms underlying the Genesis and evolution of Asthma). A standardised clinical history was completed for each patient. Cluster analysis was performed using the kernel k-groups algorithm. RESULTS: Four clusters were identified. Cluster 1 (31.5% of subjects) includes adult-onset atopic patients with better lung function, lower BMI, good asthma control, low ICS dose, and few exacerbations. Cluster 2 (23.6%) is made of adolescent-onset atopic asthma patients with normal lung function, but low adherence to treatment (59% well-controlled) and smokers (48%). Cluster 3 (17.1%) includes adult-onset patients, mostly severe non-atopic, with overweight, the worse lung function and asthma control, and receiving combination of treatments. Cluster 4 (26.7%) consists of the elderly-onset patients, mostly female, atopic (64%), with high BMI and normal lung function, prevalence of smokers and comorbidities. CONCLUSION: We defined four phenotypes of asthma using unsupervised cluster analysis. These clusters are clinically relevant and differ from each other as regards FEV1, age of onset, age, BMI, atopy, asthma severity, exacerbations, control, social class, smoking and nasal polyps.

Disposition of Work-Related Asthma in a Spanish Asthma Cohort: Comparison of Asthma Severity Between Employed and Retired Workers.

BACKGROUND: Exposure to certain agents in the workplace can trigger occupational asthma or work-exacerbated asthma, both of which come under the heading of work-related asthma (WRA). Understanding the burden that WRA represents can help in the management of these patients. OBJECTIVE: To assess the influence of occupation on asthma in real life and analyze the characteristics of patients with WRA included in an asthma cohort. METHODS: This was a prospective multicenter study of a cohort of consecutive patients with asthma. A standardized clinical history was completed. Patients were classified as having WRA or non-WRA. All patients underwent respiratory function tests, FeNO test, and methacholine challenge (methacholine concentration that causes a 20% drop in FEV1) at the beginning of the study. They were classified into two groups, depending on their employment status: employed (group 1) or unemployed (group 2). RESULTS: Of the 480 patients included in the cohort, 82 (17%) received the diagnosis of WRA. Fifty-seven patients (70%) were still working. Mean age (SD) was 46 (10.69) years in group 1 and 57 (9.91) years in group 2 (P < .0001). Significant differences were observed in adherence to treatment (64.9% in group 1 vs 88% in group 2; P = .0354) and in severe asthma exacerbations (35.7% in group 1 vs 0% in group 2; P = .0172). No significant differences were observed in the rest of the variables analyzed. CONCLUSIONS: The burden of WRA in specialized asthma units is not negligible. The absence of differences in the severity of asthma, the treatment administered, alterations in lung function, and the number of exacerbations in those working versus not working may support the idea that advice regarding changing jobs should be customized for individual patients.

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study.

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February-June 2020; n = 769 (66%)) and later (July 2020-February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11-0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01-3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22-0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81-1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

Recurrent anaphylactic reactions: an uncommon debut of lymphocytic hypophysitis.

We report on a 24-year-old male, with exercise-induced asthma and intermittent abdominal pain since puberty, who suffered from recurrent anaphylactic reactions. He also complained of occasional headaches. After extensive studies he was eventually diagnosed with idiopathic anaphylaxis, once the following diagnoses had been excluded: allergic origin [foods (including ω5-gliadin), latex and drugs], hydatidosis, carcinoid syndrome, systemic mastocytosis, autonomic epilepsy, hereditary angioedema, pheocromocitoma, Meckel diverticle, medullar thyroid carcinoma, leukemia, hyper-IgE and hypereosinophilic syndromes. Given the frequency and severity of the attacks, we started off-label treatment with omalizumab, initially well tolerated. Some days after the second dose the patient started to develop recurrent urticaria. Because of these new symptoms, blood work was repeated, and elevated TSH, decreased T4, positive antithyroid antibodies and decreased cortisol levels with normal ACTH were found. The antiadrenal autoantibodies were negative. The MRI showed a slight thickening of the infundibulum, without pituitary adenoma. Suspecting an autoimmune hypophysitis, we looked for antipituitary antibodies; the result was positive. A clinical picture of recurrent anaphylactic reactions, the result of complicated adrenal crises in an asthmatic patient, was a manifestation of lymphocytic hypophysitis, a rare chronic inflammatory disease of autoimmune etiology. One year after replacement therapy had been started, the patient remained asymptomatic.

Emerging drugs for asthma.

INTRODUCTION: Current drug treatments for asthma relieve bronchospasm and airway inflammation but do not offer a cure, and symptoms return when treatment is stopped. Asthma management guidelines emphasize the importance of effective asthma treatment to achieve and maintain asthma control. However, despite widely available and effective treatments, achieving asthma control is still an unmet need for many patients. AREAS COVERED: Remarkable efforts have been made to identify the characteristic features of difficult-to-control (usually severe) asthma that are different from those described for mild-to-moderate asthma, setting the stage for the development of new and even individualized therapies. The most fascinating options of the new asthma treatments are biologic therapies, in particular monoclonal antibodies. In addition, some novel once-daily combinations of long-acting ß(2)-agonist and inhaled corticosteroids are under development. EXPERT OPINION: Asthma is a complex syndrome made up of a number of disease variants or asthma phenotypes, with different underlying pathophysiology. As different drugs target different pathways, it is necessary to determine the individual profile of pathophysiological abnormalities for each patient. Several cytokines have been implicated in the inflammatory cascades leading to the different asthma phenotypes, and the most relevant ones are discussed. The challenge in treating asthma resides precisely in its heterogeneity.

Changes in exhaled nitric oxide levels after bronchial allergen challenge.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a marker of inflammation of the airways accompanying changes in the clinical condition of asthma. Allergen exposure has been associated with a delayed elevation of FeNO. The aim of this study was to assess airway inflammation with FeNO measurements during bronchial allergen challenge (BAC), and to determine the diagnostic performance of FeNO changes. METHODS: Thirty-four patients with asthma and sensitization to inhalant allergens were studied. BAC with common or high-molecular-weight occupational aeroallergens was performed. FeNO was measured before and 24 h after BAC. Receiver operating characteristics curve was built to assess the sensitivity and specificity of increase in FeNO levels associated with BAC outcome. RESULTS: In 21 patients (61.76%) a positive asthmatic reaction (responders) was observed. A significant increase in postchallenge FeNO was observed in this group of patients compared to the group of nonresponders. A median increase (FeNO postchallenge-FeNO prechallenge) of 14.0 ppb was observed in the group of responders, whereas a -1.0 ppb change was attained in the nonresponder group (P < 0.001). The cutoff point providing maximal sensitivity and specificity for %ΔFeNO after BAC was 12%. This change in FeNO levels has a sensitivity of 0.81 and a specificity of 0.92 for predicting a positive outcome in the BAC. CONCLUSION: FeNO measurements can be used as a surrogate of airway inflammation accompanying the asthmatic reaction induced by BAC. FeNO measurements may be a useful and reliable tool in the monitoring and interpreting specific bronchial challenge test with allergens.