Asthma and pregnancy: therapeutic challenges.

PURPOSE: Asthma in pregnancy represents a complex therapeutic challenge as it can have unfavourable consequences on both the mother and the fetus. Pregnancy can have a variable impact on asthma, and there is no general rule to predict in whom is going to be better, stable or worse. On the other hand, asthma can increase the risks of fetal malformations, low birth weight or premature birth. METHODS AND RESULTS: The review of the literature regarding the asthma pathogenic maternal and fetal effects and the current therapeutic recommendations. CONCLUSIONS: A multidisciplinary team is needed to appropriately follow up a pregnant woman with asthma and this should involve a pulmonary disease physician, a neonatologist, an obstetrician and, if necessary, an allergolocist. Most of the medications used in asthma outside pregnancy can safely be used during it. An appropriate management according to existing guidelines can minimize both maternal and fetal risks.

Patient-Reported Outcome Measures in Atopic Dermatitis and Chronic Urticaria Are Underused in Clinical Practice.

BACKGROUND: Patient-reported outcome measures (PROMs) are validated and standardized tools that complement physician evaluations and guide treatment decisions. They are crucial for monitoring atopic dermatitis (AD) and chronic urticaria (CU) in clinical practice, but there are unmet needs and knowledge gaps regarding their use in clinical practice. OBJECCTIVE: We investigated the global real-world use of AD and CU PROMs in allergology and dermatology clinics as well as their associated local and regional networks. METHODS: Across 72 specialized allergy and dermatology centers and their local and regional networks, 2,534 physicians in 73 countries completed a 53-item questionnaire on the use of PROMs for AD and CU. RESULTS: Of 2,534 physicians, 1,308 were aware of PROMs. Of these, 14% and 15% used PROMs for AD and CU, respectively. Half of physicians who use PROMs do so only rarely or sometimes. Use of AD and CU PROM is associated with being female, younger, and a dermatologist. The Patient-Oriented Scoring Atopic Dermatitis Index and Urticaria Activity Score were the most common PROMs for AD and CU, respectively. Monitoring disease control and activity are the main drivers of the use of PROMs. Time constraints were the primary obstacle to using PROMs, followed by the impression that patients dislike PROMs. Users of AD and CU PROM would like training in selecting the proper PROM. CONCLUSIONS: Although PROMs offer several benefits, their use in routine practice is suboptimal, and physicians perceive barriers to their use. It is essential to attain higher levels of PROM implementation in accordance with national and international standards.

Aortic Dissection: Spectacular Survival or Nightmare?

We describe the case of a male patient who remarkably survived two severe cardiovascular events: ascending aortic dissection and descending aortic dissection two years later. Later, the third occurrence of aortic dissection, this time involving the abdominal aorta, became an absolute nightmare for the patient, progressively being complicated by periaortic hematoma and severe anemia - events that ultimately led to his death.

Assessment of Symptoms Control, Pulmonary Function and Related Quality of Life in Asthmatic Patients Treated with Extrafine Beclomethasone Dipropionate/Formoterol Fumarate 100/6 µg pMDI: Results of a Multicenter Observational Study in Romania (ALFRESCO Study).

Introduction: Asthma treatment guidelines advocate the use of long-acting beta2-agonists (LABA) in addition to inhaled corticosteroids (ICS) in patients whose asthma is uncontrolled by ICS alone. This is the first study done in Romania, which collected the real-world data on the effects of Foster® (extrafine beclomethasone dipropionate/formoterol fumarate BDP/FF in a pressurized metered-dose inhaler pMDI 100/6 µg formulation) in adult asthmatic population. Objective: We aimed to assess the asthma symptoms control, pulmonary function and quality of life parameters in a heterogeneous Romanian asthmatic adult outpatient population, treated with extrafine BDP/FF 100/6 µg pMDI. Methods: This was a prospective, multicenter, observational study involving 30 pulmonologists randomly selected from the Romanian healthcare system, which did not declare any competing interests. Recruitment period was Oct 2018 - Feb 2019, while the patients' observational period was 24 weeks. The study included poorly controlled and uncontrolled adult asthma outpatients treated with non-extrafine formulations medication, for which the treatment indication, according to Global Initiative for Asthma (GINA) 2018, was the use of an ICS-LABA combination. The study collected demographic data, smoking habits, comorbidities, data regarding asthma diagnosis, the evolution of asthma symptoms, spirometry, Asthma Control Questionnaire (ACQ-7) scoring test, current and concomitant treatment. Results: Of 302 included patients, 290 completed the study. Pulmonary function parameters assessed during the trial (forced expiratory volume in one second - FEV1 and forced vital capacity - FVC) showed a significant improvement versus baseline (p<0.001). ACQ-7 score decreased significantly from 3.09±0.83 (visit 1) to 1.56±0.89 (visit 2) and to 1.09±0.81 (visit 3) (p<0.001). At the end of the study, 127 (43.79%) patients were well controlled (ACQ-7 score < 0.75). Conclusion: This observational study demonstrates the effectiveness and safety of extrafine fixed combination of BDP/FF (100/6 µg) pMDI in Romanian adult asthma patients uncontrolled with non-extrafine medication in a real-world setting, leading to clinically and statistically improvements in asthma control and pulmonary function.

Romanian Guidelines for the Diagnosis and Treatment of GERD-induced Respiratory Manifestations.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is a common condition present in daily practice with a wide range of clinical phenotypes. In this line, respiratory conditions may be associated with GERD. The Romanian Societies of Gastroenterology and Neurogastroenterology, in association with the Romanian Society of Pneumology, aimed to create a guideline regarding the epidemiology, diagnosis and treatment of respiratory conditions associated with GERD. METHODS: Delphi methodology was used and eleven common working groups of experts were created. The experts reviewed the literature according to GRADE criteria and formulated 34 statements and recommendations. Consensus (>80% agreement) was reached for some of the statements after all participants voted. RESULTS: All the statements and the literature review are presented in the paper, together with their correspondent grade of evidence and the voting results. Based on >80% voting agreement, a number of 22 recommendations were postulated regarding the diagnosis and treatment of GERD-induced respiratory symptoms. The experts considered that GERD may cause bronchial asthma and chronic cough in an important number of patients through micro-aspiration and vagal-mediated tracheobronchial reflex. GERD should be suspected in patients with asthma with suboptimal controlled or after exclusion of other causes, also in nocturnal refractory cough which needs gastroenterological investigations to confirm the diagnosis. Therapeutic test with double dose proton pump inhibitors (PPI) for 3 months is also useful. GERD induced respiratory conditions are difficult to treat; however,proton pump inhibitors and laparoscopic Nissen fundoplication are endorsed for therapy. CONCLUSIONS: This guideline could be useful for the multidisciplinary management of GERD with respiratory symptoms in current practice.

Bronchoalveolar lavage fluid cellular profile in workers exposed to chrysotile asbestos.

The cellular profile of bronchoalveolar lavage fluid (BALF) in asbestos-exposed population remains controversial. We, therefore, aimed to investigate BALF in apparently healthy individuals that were exposed in asbestos-related work for a long period of time. Participants were selected among employees of a car brakes and clutches factory that used chrysotile asbestos. Selection criteria were an employment history of ≥ 15 years and the absence of severe respiratory disease. The total number and type of BALF cells, the existence of dust cells, iron-laden macrophages and asbestos bodies were assessed. Thirty-nine workers (25 men), with a mean age of 46.2 ± 4.2 years and a mean employment time of 23.5 ± 4 years, participated. Asbestos bodies were observed in 14 out of 39 (36%) specimens, dust cells in 37 and iron-laden macrophages in all. Those with asbestos bodies had at least 3 times higher probability to have lymphocytosis (lymphocytes > 11%: 64% vs 28%, p = 0.027) and had an increased percentage of iron-laden macrophages compared to those without asbestos bodies (median values: 42% vs 13%, p = 0.08). Smokers (36%) had less lymphocytes compared to non and ex-smokers (median values: 6% vs. 13%, p = 0.002), and iron-laden macrophages count had a positive relation (r = 0.31, p = 0.05) to lymphocyte count. Asbestos-exposed asymptomatic individuals with the presence of asbestos bodies in the BALF are more likely to have lymphocytic alveolitis while concurrent dust exposure and smoking habits hold a significant role.

Evaluating revefenacin as a therapeutic option for chronic obstructive pulmonary disease.

INTRODUCTION: In chronic obstructive pulmonary disease (COPD), inhaled long-acting antimuscarinic agents (LAMA) are effective maintenance therapies used across all severity stages of the disease. Most of them are administered via dry powder inhalers, but these devices require a potent inspiratory flow which cannot be effectively achieved by patients with advanced disease. In such patients, inhaled therapy via nebulization might be an option. AREAS COVERED: Revefenacin is a LAMA that was specifically formulated for once daily nebulization and which was authorized by the FDA as a maintenance therapy for COPD. In phase II and III clinical studies discussed in this review, revefenacin demonstrated its rapid onset of action and sustained effect on lung function on both a short- and long-term basis. EXPERT OPINION: Nebulized revefenacin with once daily use does not require any particular effort of administration and hence can be used by patients with severe airways obstruction or by those having milder cognitive deficits. Further studies are needed, however, to better document the long-term cardiovascular safety and its ability to reduce the exacerbation rate.

Romanian clinical guideline for diagnosis and treatment of COPD.

Chronic obstructive pulmonary disease (COPD) is a disease with increasing prevalence and burden for health systems worldwide. Every country collects its own epidemiological data regarding COPD prevalence, morbidity and mortality while taking steps to educate the population and medical community to improve early detection and treatment. The rising COPD prevalence creates a need for comprehensive guidelines. In 2012 and 2017-2018, the Romanian Society of Pneumology (SRP) organised national inquiries for COPD, while lung physicians in Romania began receiving education regarding the correct algorithms for COPD diagnosis and therapy. During 2019, a Romanian clinical guideline for diagnosis and treatment of COPD was published, and a condensed version of key points from this guideline are presented herein. COPD is diagnosed based on the presence of three major components: relevant exposure history, respiratory symptoms, and airway limitation that is not fully reversible. Clinical evaluation of patients diagnosed with COPD should include the level of symptoms, exacerbation rate, the presence of comorbidities and determination of phenotypes. The present abridged guideline is designed to be accessible and practical for assessing and managing patients with COPD. The application of up-to-date COPD guidelines may enhance the optimism of physicians and patients in managing this disease.

Use of mucolytics in COPD: A Delphi consensus study.

BACKGROUND: International guidelines recommend mucolytic agents as add-on therapy in selected patients with COPD because they may reduce exacerbations and improve health status. As the evidence varies among mucolytic agents, we used the Delphi method to assess consensus amongst an international panel of COPD experts on mucolytics use in COPD. METHODS: 53 COPD experts from 12 countries were asked to complete an online questionnaire and rate their agreement with 15 statements using a 5-point scale. The mucolytic agents evaluated were carbocysteine, erdosteine and N-acetylcysteine (NAC). Data were collected anonymously and consensus presented using descriptive statistics. RESULTS: The 47 respondents reached consensus on the statements. They agreed that regular treatment with mucolytic agents effectively reduces the frequency of exacerbations, reduces the duration of mild-to-moderate exacerbations, and can increase the time to first exacerbation and symptom-free time in COPD patients. Consensus was consistently highest for erdosteine. The experts agreed that all three mucolytics display antioxidant and anti-inflammatory activity. Erdosteine and NAC were thought to improve the efficacy of some classes of antibacterial drugs. All three mucolytics were considered effective for the short-term treatment of symptoms of acute exacerbations when added to other drugs. The panel agreed that approved doses of mucolytic agents have favorable side-effect profiles and can be recommended for regular use in patients with a bronchitic phenotype. CONCLUSIONS: Consensus findings support the wider use of mucolytic agents as add-on therapy for COPD. However, the differences in pharmacological actions and clinical effectiveness must be considered when deciding which mucolytic to use.

Protocol for the EARCO Registry: a pan-European observational study in patients with α1-antitrypsin deficiency.

RATIONALE AND OBJECTIVES: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that leads to an increased risk of emphysema and liver disease. Despite extensive investigation, there remain unanswered questions concerning the natural history, pathophysiology, genetics and the prognosis of the lung disease in association with AATD. The European Alpha-1 Clinical Research Collaboration (EARCO) is designed to bring together researchers from European countries and to create a standardised database for the follow-up of patients with AATD. STUDY DESIGN AND POPULATION: The EARCO Registry is a non-interventional, multicentre, pan-European, longitudinal observational cohort study enrolling patients with AATD. Data will be collected prospectively without interference/modification of patient's management by the study team. The major inclusion criterion is diagnosed severe AATD, defined by an AAT serum level <11 µM (50 mg·dL-1) and/or a proteinase inhibitor genotype ZZ, SZ or compound heterozygotes or homozygotes of other rare deficient variants. Assessments at baseline and during the yearly follow-up visits include lung function testing (spirometry, body plethysmography and diffusing capacity of the lung), exercise capacity, blood tests and questionnaires (symptoms, quality of life and physical activity). To ensure correct data collection, there will be designated investigator staff to document the data in the case report form. All data will be reviewed by the EARCO database manager. SUMMARY: The EARCO Registry aims to understand the natural history and prognosis of AATD better with the goal to create and validate prognostic tools to support medical decision-making.

Inhaled therapies in patients with moderate COPD in clinical practice: current thinking.

COPD is a complex, heterogeneous condition. Even in the early clinical stages, COPD carries a significant burden, with breathlessness frequently leading to a reduction in exercise capacity and changes that correlate with long-term patient outcomes and mortality. Implementation of an effective management strategy is required to reduce symptoms, preserve lung function, quality of life, and exercise capacity, and prevent exacerbations. However, current clinical practice frequently differs from published guidelines on the management of COPD. This review focuses on the current scientific evidence and expert opinion on the management of moderate COPD: the symptoms arising from moderate airflow obstruction and the burden these symptoms impose, how physical activity can improve disease outcomes, the benefits of dual bronchodilation in COPD, and the limited evidence for the benefits of inhaled corticosteroids in this disease. We emphasize the importance of maximizing bronchodilation in COPD with inhaled dual-bronchodilator treatment, enhancing patient-related outcomes, and enabling the withdrawal of inhaled corticosteroids in COPD in well-defined patient groups.

Nivolumab for advanced non-small cell lung cancer: an evaluation of a phase III study.

Lung cancer still remains associated with a high mortality rate and more efficacious therapies are needed in order to improve the disease outcome. Nivolumab is a monoclonal antibody which blocks the programmed death-1 receptor which is currently evaluated in phase III clinical trials in advanced lung cancer. Here, we evaluate the results of a phase III study in which nivolumab efficacy and safety were compared to those of docetaxel. Nivolumab was able to improve survival and progression-free survival and exhibited a very good safety profile. Further clinical data are needed in order to better position this therapy among the existing methods. The promising results support the use of this therapy as a stand-alone approach.

Air pollution and respiratory diseases ­ a problematic risk factor.

Pollution was a neglected factor for years in all the research that took in the viewfinder was examined in the risk factors in of respiratory diseases. Considering the concerns of politicians, scientists, doctors, which have intensified upgraded especially after the last climate "summit", "summit" climatological we found it necessary to have a review of the effects of pollution, pathogenic mechanisms of interaction, and some diseases strongly influenced by pollutants such as COPD, asthma, bronchialand bronchial and lung cancer.

Influence of smoking on sleep and obstructive sleep apnea syndrome.

The various ill effects that tobacco smoking has on health have been largely studied, particularly on vascular, neoplastic, and respiratory diseases. Lately, the discussion about the negative impact of cigarette smoking moved towards sleep medicine. Tobacco consumption has been associated with sleep disordered architecture, both during regular intake and after withdrawal. Its effects on sleep disordered breathing (SDB) and especially obstructive sleep apnea syndrome (OSAS) still remain a matter of debate. It is unclear whether smoking represents a risk factor for OSAS or whether smoking cessation has any beneficial effects on OSAS and its therapy. There seems to be a synergistic effect between smoking and OSAS, both causing an increase in cardiovascular morbidity. Future studies are needed in order to establish the strength of this association. We aim to review the literature regarding the consequences of smoking on sleep architecture and SDB, adding emphasis on OSAS clinical implications and treatment.

Pollution and respiratory consequences--Have we done enough?

Pollution is the second major cause for many respiratory diseases, after smoking. For every country it is a challenging problem to diminish the exposure of their citizens. The authors are discussing the history of progressing of pollution in different countries, the interactions with some respiratory diseases, the influence on mortality and morbidity and the strategies in developing and developed countries for diminishing the level of the polluted particles.

Mediastinal fibrosis and Hodgkin lymphoma mimicking bronchiolitis obliterans organizing pneumonia.

Bronchiolitis obliterans organizing pneumonia (BOOP) represents a kaleidoscope of concepts and morphologies, often being confused with a series of conditions, among which the most feared are Hodgkin's lymphoma and bronchioloalveolar carcinoma. We shall present the case of a 56-year-old patient, diagnosed in August 2013 with a pulmonary tumour of the right upper lobe, which was CTstaged - T4N0M0 (IIIA), who underwent a video-assisted thoracotomy for histopathological confirmation. A mediastino-pulmonary formation had been detected intraoperatively and multiple biopsies had been collected. The information brought by the histopathological examination suggested the presence of 2 synchronous pathologies, namely: the mediastinal biopsy showed an advanced degree of dense, compact fibrosis and the pulmonary biopsy highlighted the presence of granulation tissue and Masson bodies in the distal airspace with destruction of vascular and alveolar structures, an aspect which was compatible with organizing pneumonia (BOOP). Once a diagnosis was established, an oral corticosteroid therapy was initiated (Prednisone 30 mg/day) over a period of one month, but the symptomatology of the patient worsened. A new thoracic CT carried out in November 2013 highlighted the progression and extension of the paramediastinal tumoral formation, exhibiting central necrosis and invading the mediastinal vessels, causing their compression (superior vena cava syndrome) associated with multiple mediastinal and hilar adenopathies. The non-favorable evolution and the extensive array of conditions that may mimic the BOOP histopathological pattern have been the key elements, which were the basis of our persistence in getting a real diagnosis. Therefore, in this respect, the biopsy parts performed by thoracotomy were sent for immunohistochemical testing. The CD30 and CD15 positive markers distinctive for Reed-Sternberg cells allowed the diagnosis of Hodgkin's lymphoma.

[Tiotropium in asthma--a new opportunity?]. / Tiotropium in astmul bronsic--o noua oportunitate?

Tiotropium, after years of study, began to find place among asthma medications. The authors analyze all the benefits and limitations of existing studies and try to position the 2014 indications of tiotropium in two types of conditions: asthma-COPD overlap syndrome and moderate and severe asthma.

[Does the electronic cigarette have a future in medicine?]. / Tigara electronica are vreun viitor în medicina?

The electronic cigarette is a subject of lively debate in the literature and the legislative. We will review the updates regarding progress on this issue by analyzing the device, the electronic cigarette composition, legislative issues and medical strategy. All will be analyzed in terms of the benefits, but also the immediate and remote consequences

Combined long-acting bronchodilator single therapy for COPD.

INTRODUCTION: In COPD, the long-acting bronchodilators are not always able to provide an appropriate bronchodilator effect in terms of amplitude and duration and this can result in increased severity of respiratory symptoms and in worsening of health status. Combined long-acting bronchodilators can address this limitation. AREAS COVERED: Analysis of a recent study evaluating the efficacy and safety of 26 weeks of therapy with glycopyrronium+indacaterol single inhaler (QVA149) versus each component, versus tiotropium and versus placebo. EXPERT OPINION: Such a combination can provide a superior and sustained bronchodilator effect and can minimize the respiratory symptoms resulting from a suboptimally inhibited bronchoconstriction.