Preoperative frailty screening in elderly patients with non-small cell lung cancer surgery: an essential step for a good surgical outcome.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is a disease commonly diagnosed in the elderly, often in advanced stages. However, elderly patients with lung cancer can benefit from surgery, provided that postoperative risks are assessed appropriately before surgery. Frailty is a measure of age-related impaired functional status and a predictor of mortality and morbidity. However, its importance as a preoperative marker is not well defined. AREAS COVERED: This systematic review discusses the importance of preoperative frailty screening in elderly patients with NSCLC. A literature search was performed on the MEDLINE database in June 2023, and relevant studies on frailty or preoperative assessment of NSCLC which were published between 2000 and 2023 were retained and discussed in this review. EXPERT OPINION: Among the types of existing methods used to assess frailty those on the geriatric assessment seem to be the most appropriate; however, they are unable to fully capture the 'surgical' frailty; thus, other instruments should be developed and validated in NSCLC.

Navafenterol for chronic obstructive pulmonary disease therapy.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a prevalent disease of the airways in which inhaled bronchodilators can be given as monotherapy or fixed dose combination, in order to better control disease symptoms and to reduce its morbidity. A novel bronchodilator approach is represented by bifunctional molecules such as navafenterol, which exert dual synergic bronchodilator effects as a monotherapy. Navafenterol is currently being investigated for COPD. AREAS COVERED: This review summarizes the preclinical data regarding navafenterol synthesis and in vitro and in vivo testing. Clinical data coming from phase I and II studies are also discussed. Navafenterol was found to improve lung function, dyspnea, and cough severity and was well tolerated, and its effect was comparable with that of fixed-dose combinations in patients with moderate-to-severe COPD. EXPERT OPINION: Despite clinical evidence of efficacy for navafenterol is still limited, the existing data prompts further clinical evaluation and also consideration of other inhalation approaches such as pressure metered-dose inhalers (pMDIs) or nebulization. Other interesting approach would be combination with another bifunctional molecule such as ensifentrine.

Development and Validation of a Questionnaire to Assess Knowledge and Attitudes toward COVID-19 Preventive Measures in Romania.

The World Health Organization warns about the threat of the COVID-19 sixth wave. Our aim was to propose the first validated Romanian questionnaire to assess people's level of education and attitudes towards general measures to protect against COVID-19 infection. Our study was conducted on a sample of 194 people. The first version of the questionnaire consisted of 40 items. Items that did not meet psychometric criteria were removed. Latent components/factors were identified through exploratory factorial analysis (EFA). The Cronbach's alpha coefficient was used to assess internal fidelity. The EFA identified three factors. Factor 1 was named "Compliance with protective measures", factor 2 was "Attitudes toward vaccination" and factor 3 was "Attitudes regarding potential COVID-19 therapies". The final version of the questionnaire consists of 16 items. The test's final score predicted the presence of vaccination with an accuracy of 0.773. The questionnaire score, the diagnosis of diabetes, the advice provided by healthcare workers and the medical profession proved to be significant predictors of vaccination. The implementation of our questionnaire within national programs could identify populational areas that need specific interventions to reach vaccination targets and prevent a full-blown sixth wave of the COVID-19 pandemic in Romania.

Determinants of the Hesitancy toward COVID-19 Vaccination in Eastern European Countries and the Relationship with Health and Vaccine Literacy: A Literature Review.

Herd immunity is necessary to control the coronavirus disease 2019 (COVID-19) pandemic. However, a low proportion of vaccinated people and low levels of vaccine acceptance have been noted in Eastern Europe. Our paper aimed to review the central attitudes associated with the hesitancy toward COVID-19 vaccination specific to Eastern European countries. The main Eastern European determinants of COVID-19 vaccine acceptance identified from the included studies are: public confidence in the vaccines' safety and efficacy, vaccine literacy, and public trust in the government and the medical system. Each of these determinants is discussed along with possible improvement measures. Variables specific to Eastern Europe that predict the willingness to vaccinate have also been highlighted. The specific attitudes and their context as identified by our review should be incorporated into local public health programs, with the ultimate goal of reducing viral spreading, mutation emergence, and COVID-19 morbidity and mortality both within the borders of Eastern Europe and beyond.

Primary Non-Hodgkin Uterine Lymphoma of the Cervix: A Literature Review.

Introduction: Non-Hodgkin lymphomas (NHL) comprise 85% of the total lymphomas diagnosed, with the histological type of diffuse large B-cell lymphomas (DLBCL) being the most prevalent in adults. In about 40% of cases, the location is extranodal. Uterine cervix lymphomas of this type are extremely rare (0.5-1.5%) and represent a diagnostic challenge. A case of DLBCL of the cervix is presented here along with a review of the literature. Materials and methods: A 75-year-old patient was referred with a bleeding vegetant tumour occupying her entire vagina. The histological and pathological investigations performed following the tumour biopsy indicated a malignant, diffuse, vaguely nodular lymphoid tumour proliferation. The immunohistochemistry results were in favour of a diffuse B-cell non-Hodgkin lymphoma (DLBCL). CHOP (Cyclophosphamide, Hydroxydaunorubicin (also called doxorubicin or adriamycin), Oncovin (vincristine), Prednisone or Prednisolone) polychemotherapy and radiotherapy were effective and resulted in tumour regression (from 3.4 cm to tumour disappearance, with the cervix returning to normal size). Conclusions: The uterine cervix lymphoma prognosis is more conservative than that for a nodal lymphoma, mainly due to a later diagnosis determined via immunohistochemistry. Chemotherapy is the main treatment.

Inhaled interferons beta and SARS-COV2 infection: a preliminary therapeutic perspective.

INTRODUCTION: SARS-COV2 infection represents a therapeutic challenge due to the limited number of effective therapies available and due to the fact that it is not clear which host response in terms of inflammation pattern is the most predictive for an optimal (and rapid) recovery. Interferon ß pathway is impaired in SARS-COV2 infection and this is associated with a bigger disease burden. Exogenous inhaled interferon might be beneficial in this setting. AREAS COVERED: Nebulized interferon-ß is currently investigated as a potential therapy for SARS-COV2 because the available data from a phase II study demonstrate that this medication is able to accelerate the recovery from disease. EXPERT OPINION: Further clinical studies are needed in order to better document the efficacy of this therapy especially in severe forms of COVID-19, the optimal duration of therapy and if such a medication is appropriate for domiciliary use. Also combined regimens with antivirals or with compounds which are able to enhance the endogenous production of interferon might be of promise.

COVID-19 vaccination in patients with multiple sclerosis receiving disease-modifying therapies: pragmatic issues.

The SARS-COV-2 pandemic has been a global public health problem since 2019, with over 400 million reported cases, 6 million deaths, and significant economic and social damage. Overlapping SARS-CoV-2 infection in patients with chronic diseases, such as multiple sclerosis (MS), causes management problems, especially in patients treated with disease-modifying therapies. Studies investigating COVID-19 vaccination effectiveness have shown variability in postvaccination immune response that depends on the patient's background treatment, and special attention is required for anti-CD20 therapies. Existing data on the efficacy of COVID-19 vaccination in patients with MS undergoing disease-modifying treatment are summarized and critically evaluated in this article.

Marine-Derived Compounds for the Potential Treatment of Glucocorticoid Resistance in Severe Asthma.

One of the challenges to the management of severe asthma is the poor therapeutic response to treatment with glucocorticosteroids. Compounds derived from marine sources have received increasing interest in recent years due to their prominent biologically active properties for biomedical applications, as well as their sustainability and safety for drug development. Based on the pathobiological features associated with glucocorticoid resistance in severe asthma, many studies have already described many glucocorticoid resistance mechanisms as potential therapeutic targets. On the other hand, in the last decade, many studies described the potentially anti-inflammatory effects of marine-derived biologically active compounds. Analyzing the underlying anti-inflammatory mechanisms of action for these marine-derived biologically active compounds, we observed some of the targeted pathogenic molecular mechanisms similar to those described in glucocorticoid (GC) resistant asthma. This article gathers the marine-derived compounds targeting pathogenic molecular mechanism involved in GC resistant asthma and provides a basis for the development of effective marine-derived drugs.

Challenges in Diagnosing Occupational Chronic Obstructive Pulmonary Disease.

Occupational chronic obstructive pulmonary disease (oCOPD) represents 15-20% of the global burden of this disease. Even if industrial bronchitis has long been known, new occupational hazards continue to emerge and enlarge the number of people exposed to risk. This review discusses the challenges related to the early detection of oCOPD, in the context of new exposures and of limited usage of methods for an efficient disease occupational screening. It underlines that a better translation into clinical practice of the new methods for lung function impairment measurements, imaging techniques, or the use of serum or exhaled breath inflammation biomarkers could add significant value in the early detection of oCOPD. Such an approach would increase the chance to stop exposure at an earlier moment and to prevent or at least slow down the further deterioration of the lung function as a result of exposure to occupational (inhaled) hazards.

Frailty, a Dimension of Impaired Functional Status in Advanced COPD: Utility and Clinical Applicability.

Background and Objectives: In advanced chronic obstructive pulmonary disease (COPD), functional status is significantly impaired mainly as a result of disease related respiratory symptoms such as dyspnea or as a result of fatigue, which is the extra-respiratory symptom the most prevalent in this setting. "Physical" frailty, considered to be an aging phenotype, has defining traits that can also be considered when studying impaired functional status, but little is known about this relationship in advanced COPD. This review discusses the relevance of this type of frailty in advanced COPD and evaluates it utility and its clinical applicability as a potential outcome measure in palliative care for COPD. Materials and Methods: A conceptual review on the functional status as an outcome measure of mortality and morbidity in COPD, and an update on the definition and traits of frailty. Results: Data on the prognostic role of frailty in COPD are rather limited, but individual data on traits of frailty demonstrating their relationship with mortality and morbidity in advanced COPD are available and supportive. Conclusions: Frailty assessment in COPD patients is becoming a relevant issue not only for its potential prognostic value for increased morbidity or for mortality, but also for its potential role as a measure of functional status in palliative care for advanced COPD.

Pharmacological strategies for smoking cessation in patients with chronic obstructive pulmonary disease: a pragmatic review.

Introduction: Chronic obstructive pulmonary disease (COPD) is progressive inflammatory disease of the lungs in which smoking plays a significant pathogenic role. Smoking cessation is the only therapeutic intervention which was demonstrated to interfere with disease progression. Smoking cessation intervention can benefit from pharmacological therapies such as nicotine replacement therapies, bupropion, or varenicline which can be given individually or in combination, their effectiveness being demonstrated in various clinical trials enrolling COPD patients.Areas covered: The authors provide a pragmatic discussion of the clinical data of the main studies evaluating therapies for smoking cessation within COPD starting with the seminal Lung Health Study and continuing with more recent ones.Expert opinion: Smoking cessation is one of the most difficult therapeutic interventions in COPD, despite having the highest impact on disease progression and despite the demonstrated benefit of the discussed pharmacological therapies. Potential approaches to maximize its chance of success might be represented by prolonging the time of administration, combinational options, or sequential pharmacotherapy.

Pulmonologists Adherence to the Chronic Obstructive Pulmonary Disease GOLD Guidelines: A Goal to Improve.

Background and objectives: Data about pulmonologist adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines showed a great variability and cannot be extrapolated. The present study investigates the current pharmacological prescribing practices in the treatment of chronic obstructive pulmonary disease (COPD) according to the 2017 GOLD guidelines, to determine the level of pulmonologist adherence and to identify possible factors that influence physician adherence. Materials and methods: This retrospective study took place between 1 February and 30 April 2018 in Pneumophtysiology Clinical Hospital Cluj-Napoca. We included 348 stable COPD outpatients classified according to the 2017 GOLD strategy in the ABCD risk groups. Pulmonologist adherence was defined as appropriate if the recommended pharmacological therapy was the first- or alternative-choice drug according to the guidelines, and inappropriate (overtreatment, undertreatment) if it was not in line with these recommendations. Results: The most prescribed treatment was the combination long-acting beta agonist (LABA) + long-acting antimuscarinic agent (LAMA) (34.77%), followed by LAMA + LABA + inhaled corticosteroid (ICS). Overall, pneumologist adherence was 79.02%. The most inappropriate therapies were in Group B (33.57%), followed by 33.33% in Group A. Compared to Groups C and D (analyzed together), Groups A and B had a 4.65 times higher chance (p = 0.0000001) of receiving an inappropriate therapy. Patients with cardiovascular comorbidities had a 1.89 times higher risk of receiving an inappropriate therapy (p = 0.021). ICS overprescription was the most common type of inappropriateness (17.81%). Groups C and D had a 3.12 times higher chance of being prescribed ICS compared to Groups A and B (p = 0.0000004). Conclusions: Pulmonologist adherence to the GOLD guidelines is not optimal and needs to be improved. Among the factors that influence the inappropriateness of COPD treatments, cardiovascular comorbidities and low-risk Groups A and B are important. ICS represent the most prescribed overtreatment. Further multicentric studies are needed to evaluate all factors that might influence the adherence rate.

Pharmacotherapy options in pulmonary alveolar proteinosis.

INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a heterogeneous group of rare diseases characterized by the abnormal production and impaired degradation of pulmonary surfactant as a result of malfunctioning of alveolar macrophages. This is due to the downstream dysregulation of the GM-CSF pathway, which can be caused by specific autoantibodies (autoimmune, aPAP formerly known as idiopathic iPAP), direct injury to alveolar macrophages (e.g. by toxic inhaled agents.), or by genetic defects (hereditary or congenital PAP). Few pharmacotherapy options are currently available to treat this disease. AREA COVERED: The authors discuss the exogenous administration of GM-CSF, rituximab, and the potential role of cholesterol lowering medications in this review. The authors, furthermore, provide their opinion on the available pharmacotherapeutic options and give their future perspectives. EXPERT OPINION: Inhaled GM-CSF remains the most commonly used therapy in patients with iPAP but other inhaled therapies such as PPARγ activators should be considered, especially in patients who are partially responsive or unresponsive to traditional treatments.

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.

Extra-respiratory symptoms in patients hospitalized for a COPD exacerbation: Prevalence, clinical burden and their impact on functional status.

INTRODUCTION: In COPD management, the improvement of the health status by alleviating respiratory symptoms is among the main aims. However, little is known on the prevalence and burden of extra-respiratory symptoms which can also be distressing especially during a COPD exacerbation. OBJECTIVES: To evaluate the prevalence of extra-respiratory symptoms and their impact on health and functional statuses in patients hospitalized for a COPD exacerbation. METHODS: Health status was evaluated with the COPD Assessment Test (CAT), functional status with Karnofsky index, and presence and severity of respiratory symptoms were evaluated with Edmonton Symptom Assessment Scale (ESAS). RESULTS: In a sample of 47 patients, fatigue was found to be the most prevalent 95.7% followed by pain 74.5%, lack of appetite 72.3%, depression and anxiety (each in 63.8%), drowsiness 59.6% and nausea 31.9%. The concomitant presence of an increasing number of symptoms (three, four, five, six or seven) was individually associated with worse health status or of functional status (eg, CAT score in patients with three most prevalent symptoms, fatigue, pain and lack of appetite 29.6 vs 25.1, P = .006 in patients without them; Karnofsky index scores in patients with the four most prevalent symptoms 52 vs 65.6, P = .001). Linear regressions confirmed that the increase in the number of concomitant extra-respiratory symptoms significantly correlated with the worsening of health/functional status. In conclusion, the burden of extra-respiratory symptoms in patients with hospitalized for a COPD exacerbation is significant and impact significantly on health/functional status.

Investigational inhaled therapies for non-CF bronchiectasis.

INTRODUCTION: Bronchiectasis not related to cystic fibrosis (non-CF bronchiectasis) are associated with a high unmet therapeutic need due to the lack of specifically authorized medications, especially via the inhalation route. In non-CF bronchiectasis chronic infection with Pseudomonas aeruginosa is common and favored by the persistent local inflammation and viscid sputum production. Therefore inhaled antibiotics, mucolytics or anti-inflammatory agents could represent appropriate therapeutic interventions in this setting. AREAS COVERED: This review herein discusses the inhaled therapies currently under investigation for non-CF bronchiectasis and their potential therapeutic positioning in exacerbation versus stable state. EXPERT OPINION: Inhaled antipseudomonal antibiotics are of promising efficacy, but further efforts should also be made to detect bactericidal approaches against Burkholderia cepacia complex, and to interfere chronic inflammation topically.

Benralizumab as a potential treatment of asthma.

INTRODUCTION: Current anti-inflammatory asthma therapies including inhaled corticosteroids and leukotriene modifiers, are not always able to appropriately control the disease and other approaches are needed. These therapies specific target IgE (omalizumab) or IL-5 (mepolizumab). However, there is research underway investigating interleukin-based monoclonal antibodies such as benralizumab, an anti-IL-5R monoclonal antibody which is currently in phase III clinical development. Areas covered: This review summarizes the existing preclinical and clinical data of benralizumab. Data reviewed includes benralizumab's efficacy and safety data. The author also provides their expert opinion on this potential therapeutic and provide their perspectives for its future development. Expert opinion: Benralizumab was able to interfere significantly with disease-related morbidity and in particular with hospitalizations due to asthma exacerbation rates in a subset of patients with higher systemic eosinophil burden and higher doses of inhaled corticosteroids. The sustained inhibitory effect on eosinophilic inflammation might be an advantage which can be translated in less frequent dosing. Further attempts should be made to better define the asthma endotype in which such an antibody would be the most efficacious.

Lebrikizumab for the treatment of asthma.

INTRODUCTION: In asthma, most commonly, 'conventional' anti-inflammatory medications represented by inhaled corticosteroids and leukotriene inhibitors are effective. In some patients however additional inhibition of the airways inflammation is necessary. Such compounds might be molecules inhibiting specifically certain inflammation pathways and lebrikizumab an anti IL-13 molecule might represent a relevant example as a potential asthma therapy. AREAS COVERED: Discussion of the rationale for the use of lebrikizumab in asthma. Analysis of the related preclinical and clinical data on lebrikizumab in asthma. EXPERT OPINION: Lebrikizumab demonstrated efficacy in an asthma subset characterized by high serum periostin levels and by heavy eosinophilic inflammation. Phase III data are necessary in order to better position this therapy in asthma including as a potential personalized approach.

Palliative care outcome measures in COPD patients: a conceptual review.

In chronic obstructive pulmonary disease (COPD), palliative care is appropriate in very advanced stages based on recognition of its need when conventional therapy is no longer able to control symptoms, disease morbidity, or to improve/maintain an acceptable quality of life. Palliative care aims to improve quality of life, or, if applied specifically at the end-of-life, to ensure comfortable care. In COPD palliative care effectiveness of interventions should be quantified with outcome measures able to better capture the holistic nature of approaches and not only the specific features of disease. These should include: physical outcomes, psychological outcomes, social outcomes, spiritual outcomes. Such measures are discussed in this review along with arguments supporting their use.

Impact of fatigue in patients with chronic obstructive pulmonary disease: results from an exploratory study.

INTRODUCTION: Fatigue, which is also present in the healthy population, is a common but understudied symptom in chronic obstructive pulmonary disease (COPD). We hypothesized that clinically significant fatigue is also frequent in COPD and can be associated with an increased disease burden. METHODS: An exploratory analysis derived from an ongoing cross-sectional study was carried out to evaluate levels of fatigue and impact on health-related quality of life/health status in patients with COPD (COPD group; n = 20) and healthy subjects (control group; n = 5). Health-related quality of life was measured using the Short Form Health Survey 36 (SF-36), health status with the Clinical COPD Questionnaire (CCQ), and airways obstruction with postbronchodilator forced expiratory volume in 1 s (FEV1 %predicted). Fatigue was measured with the vitality score of the SF-36, its clinical significance being defined by values of 50 or less. Fatigue was also measured using the Functional Assessment of Chronic Illness Therapy scale for fatigue (FACIT-F). RESULTS: Vitality scores were significantly worse in the COPD group (45.60 versus 76.25; p = 0.004). FACIT-F scores were significantly lower in the COPD group versus the control group (74.5 versus 95.0; p = 0.03). Clinically significant fatigue was detected in 60% of the COPD group, and was associated with a worse FEV1 %predicted (47.71 versus 65.82%; p = 0.016), worse symptoms burden (CCQ symptoms score 3.75 versus 2.43; p = 0.019), and worse overall health status (CCQ total score 3.30 versus 2.11; p = 0.011). Its link with systemic inflammation remains to be clarified further. CONCLUSIONS: Clinically significant fatigue is common among patients with COPD and is associated with an increased disease burden. It should therefore be integrated as a measure of disease prognosis and control in patients with COPD.