Untreated Obstructive Sleep Apnea in Interstitial Lung Disease and Impact on Interstitial Lung Disease Outcomes.

Subjects with interstitial lung disease (ILD) often suffer from nocturnal cough, insomnia, and poor sleep quality. Subjects with ILD and obstructive sleep apnea (OSA) seem to have relatively mild symptoms from sleep fragmentation compared to subjects with only ILD. The overlap of ILD, OSA, and sleeping hypoxemia may be associated with poor outcome, even though there is no agreement on which sleep parameter is mostly associated with worsening ILD prognosis. Randomized controlled trials are needed to understand when positive airway pressure (PAP) treatment is required in subjects with ILD and OSA and the impact of PAP treatment on ILD progression.

Inhaled Corticosteroids in Subjects with Chronic Obstructive Pulmonary Disease: An Old, Unfinished History.

Chronic obstructive pulmonary disease (COPD) is one of the major causes of disability and death. Maintenance use of inhaled bronchodilator(s) is the cornerstone of COPD pharmacological therapy, but inhaled corticosteroids (ICSs) are also commonly used. This narrative paper reviews the role of ICSs as maintenance treatment in combination with bronchodilators, usually in a single inhaler, in stable COPD subjects. The guidelines strongly recommend the addition of an ICS in COPD subjects with a history of concomitant asthma or as a step-up on the top of dual bronchodilators in the presence of hospitalization for exacerbation or at least two moderate exacerbations per year plus high blood eosinophil counts (≥300/mcl). This indication would only involve some COPD subjects. In contrast, in real life, triple inhaled therapy is largely used in COPD, independently of symptoms and in the presence of exacerbations. We will discuss the results of recent randomized controlled trials that found reduced all-cause mortality with triple inhaled therapy compared with dual inhaled long-acting bronchodilator therapy. ICS use is frequently associated with common local adverse events, such as dysphonia, oral candidiasis, and increased risk of pneumonia. Other side effects, such as systemic toxicity and unfavorable changes in the lung microbiome, are suspected mainly at higher doses of ICS in elderly COPD subjects with comorbidities, even if not fully demonstrated. We conclude that, contrary to real life, the use of ICS should be carefully evaluated in stable COPD patients.

Systemic Corticosteroids for Treating Respiratory Diseases: Less Is Better, but When and How Is It Possible in Real Life?

Systemic corticosteroids (CSs), a keystone in pulmonology, are drugs with strong antiinflammatory activity. They are cheap, easily available, and accessible, but with common and serious side effects. Moreover, the use of exogenous CSs may suppress the hypothalamic-pituitary-adrenal (HPA) axis, predisposing to adrenal insufficiency. Safe CS treatment is a challenge of pharmacological research. This narrative review examined the indications of CSs in some respiratory diseases, analyzing what types, dosages, and length of treatment are required as the dosage and duration of CS treatments need to be minimized. Chronic maintenance treatments with CSs are associated with poor prognosis, but they are still prescribed in patients with severe asthma, Chronic obstructive pulmonary disease (COPD), and interstitial lung diseases. When CS discontinuation is not possible, all efforts should be made to achieve clinically meaningful reductions. Guidelines suggest the use of methylprednisolone at a dose of 20-40 mg/day or equivalent for up to 10 days in subjects with COVID-19 pneumonia (but not other respiratory viral diseases) and respiratory failure, exacerbations of asthma, and COPD. Some guidelines suggest that CS treatment shorter than 10-14 days can be abruptly stopped, strictly monitoring subjects with unexplained symptoms after CS withdrawal, who should promptly be tested for adrenal insufficiency (AI) and eventually treated. CSs are often used in severe community-acquired pneumonia associated with markedly increased serum inflammation markers, in acute respiratory distress syndrome (ARDS), in septic shock unresponsive to hydro-saline replenishment and vasopressors, and acute exacerbations of interstitial lung diseases. As these cases often require higher doses and longer duration of CS treatment, CS tapering should be gradual and, when useful, supported by an evaluation of HPA axis function.

Prognostic Significance of Obstructive Sleep Apnea in a Population of Subjects with Interstitial Lung Diseases.

INTRODUCTION: Obstructive sleep apnea (OSA) is often observed in subjects with interstitial lung disease (ILD). It may have a negative impact on the course of ILD, but its prognostic significance in relation to other known indicators of poor outcome is unclear. METHODS: After a detailed work-up, including overnight unattended type III polygraphy, all subjects newly diagnosed with ILDs referred to our clinics were followed-up for at least 1.5 years or until death or progression of disease [> 10% decline in forced vital capacity (FVC) below baseline]. We analyzed relationships between some prespecified variables of interest, including sleeping results, to establish parameters predictive of progressive course. RESULTS: Our population consisted of 46 subjects (mean age 59.6 years; males 61%); 23.9% and 41% had idiopathic pulmonary fibrosis and ILD associated with systemic diseases, respectively. Mean baseline forced vital capacity and diffusion capacity of carbon monoxide were 83% and 57% of predicted, respectively. Mean (± SE) Apnea-Hypopnea Index (AHI) was 17 (± 3) events/h. AHI in the ranges 5-14.9, 15-29.9, and ≥ 30 was recorded in 14 (31%), 6 (13%), and 9 (20%) subjects, respectively. Mean distance covered in the 6-MWG walk test (6MWT) was 302 (± 19) m and 26 subjects (57%) showed exertional oxyhemoglobin desaturation. The median follow-up was about 18 months. Multivariate logistic regression analysis showed that exertional desaturation (HR 8.2; 1.8-36.5 95% CI; p = 0.006) and AHI ≥ 30, namely the threshold of severe OSA (HR 7.5; 1.8-30.6; p = 0.005), were the only independent variables related to progressive disease course. CONCLUSION: We conclude that exertional desaturation and elevated AHI had independent negative prognostic significance in our ILD population.

No-shaking and shake-fire delays affect respirable dose for suspension but not solution pMDIs.

It has long been accepted that suspension pressurized metered-dose inhalers (pMDIs) must be shaken if a correct dose is to be delivered, if not, it will usually be higher than the label claim. The purpose of this work was to investigate the influence of the device being unshaken, shaken and after a period of delay in pMDI actuation on the Fine Particle Mass (<5 µm), Extra Fine Particle Mass (<2 µm) and MMAD. Solution and suspension commercial pMDIs containing one, two or three components were used in the study. Most of the suspension pMDIs produced variable amounts of respirable size drug following the shake-fire delays tested in terms of the label claim dose. The effect was even more critical if the inhaler was not shaken and the FPM was found to be between -82 % for Symbicort and 363 % for Ventolin compared with the control values. In the case of MMAD measurements, Seretide and Serzyl inhalers showed the largest change from around 3 µm to 4.2-5.1 µm when not shaken. Conversely, the FPM and MMAD for the solution aerosols remained unchanged whether or not they were shaken or when a progressive increase in the delay in actuation after shaking was employed.

The Acute Effects of an Ultramarathon on Atrial Function and Supraventricular Arrhythmias in Master Athletes.

BACKGROUND: Endurance sports practice has significantly increased over the last decades, with a growing proportion of master athletes. However, concerns exist regarding the potential proarrhythmic effects induced by ultra-endurance sports. This study aimed to analyse the acute effects of an ultramarathon race on atrial remodelling and supraventricular arrhythmias in a population of master athletes. METHODS: Master athletes participating in an ultramarathon (50 km, 600 m of elevation gain) with no history of heart disease were recruited. A single-lead ECG was recorded continuously from the day before to the end of the race. Echocardiography and 12-lead resting ECG were performed before and immediately at the end of the race. RESULTS: The study sample consisted of 68 healthy non-professional master athletes. Compared with baseline, P wave voltage was higher after the race (p < 0.0001), and more athletes developed ECG criteria for right atrial enlargement (p < 0.0001). Most of the athletes (97%) had ≥1 premature atrial beats (PAB) during the 24-h monitoring, also organised in triplets (17%) and non-sustained supraventricular tachycardias (NSSVTs) (19%). In contrast, exercise-induced PABs, triplets, and NSSVTs were rare. One athlete developed acute atrial fibrillation during the race. After the race, no significant differences were found in biatrial dimensions. Biatrial function, estimated by peak atrial longitudinal and contraction strains, were normal both before and after the race. CONCLUSIONS: In master athletes running an ultramarathon, acute exercise-induced atrial dysfunction was not detected, and exercise-induced supraventricular arrhythmias were uncommon. These results did not confirm the hypothesis of an acute atrial dysfunction induced by ultra-endurance exercise.

A Comprehensive Review of Sarcoidosis Diagnosis and Monitoring for the Pulmonologist.

Sarcoidosis is a systemic granulomatous disease with heterogenous clinical manifestations. Here we review the diagnosis of sarcoidosis and propose a clinically feasible diagnostic work-up and monitoring protocol. As sarcoidosis is a systemic disease, a multidisciplinary approach is recommended for best outcomes. However, since the lungs are frequently involved, the pulmonologist is often the referral physician for diagnosis and management. When sarcoidosis is suspected, diagnosis needs to be confirmed and organ involvement/impairment assessed. This process is also required to establish whether the patient is likely to benefit from treatment, as many cases of sarcoidosis are self-limited and remit spontaneously. Whether or not treatment is started, effective regular follow-up is necessary to monitor changes in the disease, including extension, progression, remissions, flare-ups, and complications.

A Comprehensive Review of Sarcoidosis Treatment for Pulmonologists.

Due to frequent lung involvement, the pulmonologist is often the reference physician for management of sarcoidosis, a systemic granulomatous disease with a heterogeneous course. Treatment of sarcoidosis raises some issues. The first challenge is to select patients who are likely to benefit from treatment, as sarcoidosis may be self-limiting and remit spontaneously, in which case treatment can be postponed and possibly avoided without any significant impact on quality of life, organ damage or prognosis. Systemic glucocorticosteroids (GCs) are the drug of first choice for sarcoidosis. When GCs are started, there is a > 50% chance of long-term treatment. Prolonged use of prednisone at > 10 mg/day or equivalent is often associated with severe side effects. In these and refractory cases, steroid-sparing options are advised. Antimetabolites, such as methotrexate, are the second-choice therapy. Biologics, such as anti-TNF and especially infliximab, are third-choice drugs. The three treatments can be used concomitantly. Regardless of whether treatment is started, the clinician needs to organize regular follow-up to monitor remissions, flares, progression, complications, toxicity and relapses in order to promptly adjust the drugs used.

Inhaler technique in asthma and COPD: challenges and unmet knowledge that can contribute to suboptimal use in real life.

Introduction: Inhalers are the most commonly used devices for lung drug delivery in asthma and COPD. Inhaler use offers several advantages but requires the user's proper mastery. The issue of inhaler technique is very important as inhaler misuse remains common in real life regardless of the inhaler used and is associated with poor disease control.Areas covered:This narrative review analyses the key-steps of inhaler mastery and the significance of the errors of use for the main devices. There are uncertainties on many tasks of inhaler use and on those variations from recommended steps that are considered as critical errors.Expert opinion: Despite technological advancements, an easy-to-use device is not yet available. Whatever the chosen inhaler, health care givers' proper practical education with the opportunity of feedback learning has a key-role for improving inhaler technique, but is time-consuming, and remains limited to few successful experiences. Newer digital technologies will be applied to the field of inhaler education, but the lack of knowledge on many practical aspects of inhaler technique might be a limit for its extensive implementation. Possibly digital innovation might substantially contribute to reduce inhaler misuse only if clinicians, manufacturers, and subjects will cooperate together on this issue.

Consequences of not-shaking and shake-fire delays on the emitted dose of some commercial solution and suspension pressurized metered dose inhalers.

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) include hydrofluoroalkane (HFA) propellant to generate a drug aerosol upon actuation and drugs can be formulated as solution or suspension. Suspended particles can cream or sediment depending on density differences between drug and propellant and shaking the pMDI is an essential step to ensure a uniform drug dose release. RESEARCH DESIGN AND METHODS: The effect of the delay (0, 10, 30, 60 seconds) in pMDI actuation after shaking and the effect of no-shaking during the canister life on the emitted dose (ED) for commercial solution and suspension pMDIs was investigated. RESULTS: The ED for solutions was unaffected by no-shaking or by the progressive increasing delay in actuation after shaking (between 77% and 97%). For all the suspension products, shaking was demonstrated to be critical to assure the close to nominal drug delivery. In detail, the actuation delay after shaking led to an increase up to 380% or a drop to 32% of ED in relation to the label claim with high variability. CONCLUSION: The drug delivered can vary widely for no-shaking and over different shake-fire delays with suspension pMDIs while solution formulations appear to remain stable.

Muscle Activation in Traditional and Experimental Barbell Bench Press Exercise: A Potential New Tool for Fitness Maintenance.

BACKGROUND: The bench press exercise (BP) is commonly practiced in both recreational and professional training. The weight is lowered from a position where the elbows are at a 90° angle at the start and <90° at the end of eccentric phase, and then returned to the elbows extended position. In order to focus the exercise more on the triceps brachii (TB) rather than the pectoralis major (PM), the inter-handle distance (IHD) is decreased diminishing the involvement of the PM in favor of the TB. PURPOSE: To improve performance of the exercise by reducing force dissociation and transmitting 100% of the external load to the muscle tissue we propose a prototype of the barbell with a bar on which two sleeves are capable of sliding. The dynamic modifications of the IHD keep the elbow flexion angle constant at 90°. RESULTS: Analysis of the inter-handle distance (IHD) signals of the upper body muscles showed a marked increase in muscle activity using the experimental barbell for the PM (19.5%) and for the biceps brachii (173%). CONCLUSIONS: The experimental barbell increased the muscle activity typical of the bench press exercise, obtaining the same training induction with a lower load and consequently preventing articular stress.

Olodaterol for the treatment of chronic obstructive pulmonary disease: a narrative review.

INTRODUCTION: Inhaled bronchodilators are the key-stone of chronic obstructive pulmonary disease (COPD) management. Olodaterol 5 µg, a long-acting ß2-adrenoceptor agonist (LABA) is one such bronchodilator indicated as a once-daily maintenance therapy. Areas covered: This article reviews the several trials that have assessed olodaterol as a COPD therapy. It covers safety and tolerability data and provides the reader with an expert opinion on its use as a treatment for COPD. Expert opinion: Olodaterol improves lung function for 24 h and reduces rescue medication use. It may also improve dyspnea, exercise tolerance, and health-related quality of life. It is well tolerated with an acceptable cardiovascular and respiratory adverse event profile. There is some evidence that olodaterol, as well as other LABAs, can reduce exacerbation frequency, but not FEV1 decline and death. LABAs alone are indicated in group A/B COPD subjects. Olodaterol and indacaterol are administered once-daily and may offer an adherence advantage over other LABAs with more frequent dosing schedules. Co-administration of an olodaterol/tiotropium fixed dose combination in a single inhaler device is recommended as step-up in group A/B COPD subjects not sufficiently treated by olodaterol alone or as initial therapy in those with severe exertional dyspnea.

Situation of Endodontics in the Public Health Service in Brazil through the Access and Quality Improvement Program (PMAQ-CEO)

Objective: To describe and analyze the situation of endodontics in the Brazilian public service. Material and Methods: Data from questions about endodontics were divided by states and regions and organized in spreadsheets for descriptive statistical analysis, with absolute and relative data. Results: It was found that the northern region of Brazil concentrates the smaller number of services (6.4%). Pre-established protocols with basic attention to the endodontics specialty are applied in 73.3% of CEOs. Overall, 24% of services use rotating instruments and 38% use apical locators; 87.4% perform endodontic treatment in teeth with 3 or more roots. In these centers, 75.7% of dentists who perform endodontics are specialists, masters or PhD in dentistry. Endodontics has the highest absenteeism rate and the longer waiting time to initiate treatment compared to the other basic specialties. Conclusion: The endodontics situation of the resulting PMAQ-CEO revealed that the specialty is the most requested, but services lack more effective management mechanisms to minimize the observed absenteeism problem by reducing existing waiting lines. The situation also revealed that endodontics services at CEOs are provided by specialists, almost half of the services perform single session treatment on vital pulp teeth and that the same proportion of CEOs use apical locators and / or rotating instruments to perform endodontic treatment. Investments in the installed capacity, permanent management and education are still needed to improve the quality of services provided to the population.

The pharmacological treatment of bronchiectasis.

INTRODUCTION: Until recently considered as a minor health problem, the role of bronchiectasis is now increasingly recognized. New specific drugs are being approved for treatment of bronchiectasis. Possibly they will offer better perspectives to bronchiectatic subjects with evolving course. Areas covered: We provide an overview of aetiopathogenesis, clinics and non-pharmacological management, extending the topic of pharmacological treatment. Present therapies were extrapolated from other chronic lung diseases, but newer promising specific drugs are being awaited. Therapy aims at improving mobilisation of bronchial secretions and, if any, reversing airflow obstruction. Antibiotics are indicated to treat exacerbations, eradicate or reduce sputum bacterial load. Expert commentary: Over the last years evidence is mounted that bronchiectatic subjects with accelerated course of disease should be referred to secondary and tertiary centres. This requires increased awareness on the role and the frequency of bronchiectasis in primary care. Long-term continuous or cyclical use of antibiotics is recommended to stabilize or improve the course of evolving disease. Macrolides are a currently preferred option. Inhaled antibiotics are gaining importance and are the object of ongoing research interest. Practical challenges of inhaled antibiotic treatment remain the need of defining the best therapeutic regimen and optimizing true adherence.

Home oxygen therapy: re-thinking the role of devices.

INTRODUCTION: A range of devices are available for delivering and monitoring home oxygen therapy (HOT). Guidelines do not give indications for the choice of the delivery device but recommend the use of an ambulatory system in subjects on HOT whilst walking. Areas covered: We provide a clinical overview of HOT and review traditional and newer delivery and monitoring devices for HOT. Despite relevant technology advancements, clinicians, faced with many challenges when they prescribe oxygen therapy, often remain familiar to traditional devices and continuous flow delivery of oxygen. Some self-filling delivery-less devices could increase the users' level of independence with ecological advantage and, perhaps, reduced cost. Some newer portable oxygen concentrators are being available, but more work is needed to understand their performances in different diseases and clinical settings. Pulse oximetry has gained large diffusion worldwide and some models permit long-term monitoring. Some closed-loop portable monitoring devices are also able to adjust oxygen flow automatically in accordance with the different needs of everyday life. This might help to improve adherence and the practice of proper oxygen titration that has often been omitted because difficult to perform and time-consuming. Expert commentary: The prescribing physicians should know the characteristics of newer devices and use technological advancements to improve the practice of HOT.

Time Required to Rectify Inhaler Errors Among Experienced Subjects With Faulty Technique.

BACKGROUND: Regardless of the device used, many patients have difficulty maintaining proper inhaler technique over time. Repeated education from caregivers is required to ensure persistence of correct inhaler technique, but no information is available to evaluate the time required to rectify inhaler errors in experienced users with a baseline faulty technique and whether this time of re-education to restore inhaler mastery can differ between devices. METHODS: This was a multi-center, single-visit, open-label, cross-sectional study in a large group of 981 adult subjects (mean ± SD age 64 ± 15 y) experienced with inhaler use, mainly suffering from COPD and asthma, who showed faulty inhaler technique at a follow-up visit in chest clinics. These subjects received face-to-face practical education from trained caregivers until proper inhaler use could be demonstrated, and the time of instruction was recorded. RESULTS: The mean times (95% CIs) in minutes of instruction required for rectifying misuse and demonstrating inhaler mastery were 5.0 (3.6-6.4) min for the Diskus (n = 199), 5.3 (3.7-6.8) min for the HandiHaler (n = 219), 8.1 (5.6-10.5) min for the metered-dose inhaler (MDI) (n = 532), and 6.0 (5.0-7.0) min for the Turbuhaler (n = 169). The time to demonstrate good inhaler use for MDIs was higher (P < .05) than for all dry powder inhalers (DPIs). Between the DPIs, only the HandiHaler required more time for achieving mastery than the Diskus (P = .005). The variables associated with increasing time for correcting inhaler errors were an older age (0.05 min/y, 95% CI 0.03-0.07), a lower level of education (0.4 min/schooling level, 95% CI 0.7-0.1), and no reported previous instruction in inhaler use (1.96 min, 95% CI 1.35-2.58). CONCLUSIONS: In experienced subjects with baseline faulty inhaler use, the mean time of education required to achieve and demonstrate mastery with DPIs was lower than with MDIs.

O ensino da Clínica Ampliada para ingressantes do curso de Odontologia: um relato de experiência / The teaching of the Expanded Clinic for Dental course first-year students: an experience report

De acordo com as Diretrizes Curriculares Nacionais para os cursos de Odontologia, a formação do Cirurgião-dentista deve resultar em um profissional capaz de atender às necessidades de saúde bucal da população e estar em consonância com os princípios do Sistema Único de Saúde. Para tanto, o ensino da clínica deve extrapolar o ato operatório e ampliar seu escopo de prática. Neste sentido, desde 2006, a Faculdade de Odontologia da Universidade de São Paulo ministra aos estudantes do primeiro semestre de graduação a Disciplina denominada Clínica Ampliada de Promoção de Saúde (CAPS), que se propõe, desde o ingresso do estudante no curso superior, a romper com o paradigma da saúde como ausência de doença e apresentar a interface entre o biológico e o social neste processo, na perspectiva da ampliação da clínica e do cuidado integral. Este relato de experiência tem o objetivo de descrever a disciplina de CAPS, caracterizando as estratégias pedagógicas e sua relevância na inserção dos estudantes nos cenários de prática na atenção básica, bem como os métodos de avaliação implementados durante o ano. Espera-se que o modelo de Disciplina apresentado possa fomentar o debate e promover discussões dentro dos cursos de Odontologia, para que o mais precocemente possível, possamos discutir com os estudantes temas relacionados ao cuidado em saúde e à clínica ampliada (AU).

According to the National Curricular Guidelines for Dental courses, the training of the dentist should result in a professional capable of meeting the oral health needs of the population and be in line with the principles of the Unified Health System. The teaching of the clinic must extrapolate the operative act and broaden its scope of practice. Since 2006, the Faculty of Dentistry of the University of São Paulo teaches the students of the first semester of graduation the subject called Expanded Health Promotion Clinic. The Subject proposes to break with the health paradigm as the absence of disease and to present the interface between the biological and the social in this process, to the expansion of the clinic and integral care. This experience report aims to describe the subject, characterizing pedagogical strategies and their relevance in the insertion of students in the practice scenarios in primary care, as well as the evaluation methods implemented during the year. It is hoped that subject model presented may stimulate debate and promote discussions within the Subject coursesso that as early as possible we can discuss the topics related to health care and the Extended Clinic (AU).

Safety of long acting muscarinic antagonists: are all these drugs always and equally safe?

Inhaled bronchodilators - such as long-acting muscarinic receptor antagonists (LAMAs) - are central to the pharmacological management of symptomatic chronic obstructive pulmonary disease. LAMAs are considered to be safe drugs at recommended dosages. In the present issue of the Journal safety of umeclidinium, a recently marketed LAMA, at twice the recommended dosage, has been evaluated with good results in a Japanese, COPD population. However, because muscarinic receptors are expressed not only in the lungs but also at the level of heart, digestive and urinary apparatus, the potential exists for LAMAs to cause adverse events related to stimulation of receptors in these organs. Head-to-head and post-marketing vigilance studies are required to determine the profile risk of these drugs, ultimately, and whether differences exist between currently available LAMAs.

Maintaining Control of Chronic Obstructive Airway Disease: Adherence to Inhaled Therapy and Risks and Benefits of Switching Devices.

Asthma and chronic obstructive pulmonary disease (COPD) are major obstructive airway diseases that involve underlying airway inflammation. The most widely used pharmacotherapies for asthma and COPD are inhaled agents that have been shown to be effective and safe in these patients. However, despite the availability of effective pharmacologic treatment and comprehensive treatment guidelines, the prevalence of inadequately controlled asthma and COPD is high. A main reason for this is poor adherence. Adherence is a big problem for all chronic diseases, but in asthma and COPD patients there are some additional difficulties because of poor inhalation technique and inhaler choice. Easier-to-use devices and educational strategies on proper inhaler use from health caregivers can improve inhaler technique. The type of device used and the concordance between patient and physician in the choice of inhaler can also improve adherence and are as important as the drug. Adherence to inhaled therapy is absolutely necessary for optimizing patient control. If disease control is not adequate despite good adherence, switching to a more appropriate inhaled therapy is recommended. By contrast, uninformed switching or switching to less user-friendly inhaler may impact disease control negatively. This critical review of the available literature is aimed to provide a guidance protocol on when a switch may be recommended in individual patients.