Disability in moderate chronic obstructive pulmonary disease: prevalence, burden and assessment - results from a real-life study.

BACKGROUND: The role of disability and its association with patient-reported outcomes in the nonsevere forms of chronic obstructive pulmonary disease (COPD) has never been explored. OBJECTIVES: The aim of this study was to assess, in a cross-sectional real-life study, the prevalence and degree of disability in moderate COPD patients and to assess its association with health status, illness perception, risk of death and well-being. METHODS: Moderate COPD outpatients attending scheduled visits were involved in a quantitative research program using a questionnaire-based data collection method. RESULTS: Out of 694 patients, 17.4% were classified as disabled and 47.6% reported the loss of at least one relevant function of daily living. Disabled patients did not differ from nondisabled patients in terms of working status (p = 0.06), smoking habits (p = 0.134) and ongoing treatment (p = 0.823); however, the former showed a significantly higher disease burden as measured by illness perception, health status and well-being. The stepwise regression analysis showed that the modified Medical Research Council (mMRC) score was the most relevant factor related to COPD disability (F = 38.248; p = 0.001). Patient stratification was possible according to the forced expiratory volume in 1 s (FEV1) value and an mMRC score ≥2, which identified disabled patients, whereas the mMRC values were differently associated with the risk of disability. CONCLUSION: A significant proportion of individuals with moderate COPD reported a limitation of daily life functions, with dyspnea being the most relevant factor inducing disability. Adding the evaluation of patient-reported outcomes to lung function assessment could facilitate the identification of disabled patients.

The current practice in the diagnostic work-up of patients with hemoptysis of unknown etiology: an international survey.

BACKGROUND: Hemoptysis is a challenging and potentially life-threatening medical condition. The most appropriate diagnostic work-up is debated and several diagnostic approaches are implemented worldwide. METHODS: An international, online survey was carried out to investigate the current practice of the diagnostic work-up of patients with hemoptysis of unknown etiology. RESULTS: Overall, 604 physicians responded to the survey. At baseline, chest X-ray was suggested as the first diagnostic investigation by 342 (56.6%) participants. Computed tomography (CT) was suggested in each patient with non- and life-threatening hemoptysis by 310 (51.3%) and 526 (87.1%) respondents, respectively. Contrast-enhanced CT is the currently preferred technique (333, 55.1%). In case of patchy ground glass opacities and negative CT, 287 (47.5%) and 222 (36.8%) participants, respectively, would always offer bronchoscopy. Otorhinolaryngological evaluation was mostly suggested in case of suspected upper airways bleeding before other investigations (212, 35.1%). A follow-up was recommended for idiopathic hemoptysis by the majority of the participants (316, 52.3%). A multidisciplinary assessment is deemed crucial for each patient with life-threatening hemoptysis (437, 72.4%). CONCLUSIONS: Chest X-ray and contrast-enhanced CT are currently preferred as the first diagnostic investigations, regardless of hemoptysis severity. Bronchoscopy is suggested in case of negative radiological examination and when CT shows only ground glass opacities. Otorhinolaryngological evaluation is advised before any other investigations when upper airways bleeding is suspected. Patients with idiopathic hemoptysis are suggested to undergo a clinical follow-up and in case of life-threatening bleeding a multidisciplinary assessment is deemed crucial. Due to the heterogeneous approaches a consensus statement would be needed.

Pneumomediastinum in COVID-19: Risk factors and outcomes from a multicentre case-control study.

BACKGROUND: An increased incidence of pneumomediastinum has been observed among patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. The study aimed to identify risk factors for COVID-19-associated pneumomediastinum and investigate the impact of pneumomediastinum on clinical outcomes. METHODS: In this multicentre retrospective case-control study, we included consecutive patients with COVID-19 pneumonia and pneumomediastinum hospitalized from March 2020 to July 2020 at ten centres; then, we identified a similarly sized control group of consecutive patients hospitalized with COVID-19 pneumonia and respiratory failure who did not develop pneumomediastinum during the same period. Clinical, laboratory, and radiological characteristics, as well as respiratory support and outcomes, were collected and compared between the two groups. Risk factors of pneumomediastinum were assessed by multivariable logistic analysis. RESULTS: Overall 139 patients with pneumomediastinum and 153 without pneumomediastinum were analysed. Lung involvement ≥75 %, consolidations, body mass index (BMI) < 22 kg/m2, C-reactive protein (CRP) > 150 mg/L, D-dimer >3000 ng/mL FEUs, and smoking exposure >20 pack-year were all independently correlated with the occurrence of pneumomediastinum. Patients with pneumomediastinum had a longer hospital stay (mean ± SD 31.2 ± 20.2 days vs 19.6 ± 14.2, p < 0.001), higher intubation rate (73/139, 52.5 % vs 27/153, 17.6 %, p < 0.001), and in-hospital mortality (68/139, 48.9 % vs 36/153, 23.5 %, p < 0.001) compared to controls. CONCLUSIONS: Extensive lung parenchyma involvement, consolidations, low BMI, high inflammatory markers, and tobacco exposure are associated with a greater risk of pneumomediastinum in COVID-19 pneumonia. This complication significantly worsens the outcomes.

Pleural Mesothelioma: Advances in Blood and Pleural Biomarkers.

Pleural mesothelioma (PM) is a type of cancer that is highly related to exposure to asbestos fibers. It shows aggressive behavior, and the current therapeutic approaches are usually insufficient to change the poor prognosis. Moreover, apart from staging and histological classification, there are no validated predictors of its response to treatment or its long-term outcomes. Numerous studies have investigated minimally invasive biomarkers in pleural fluid or blood to aid in earlier diagnosis and prognostic assessment of PM. The most studied marker in pleural effusion is mesothelin, which exhibits good specificity but low sensitivity, especially for non-epithelioid PM. Other biomarkers found in pleural fluid include fibulin-3, hyaluronan, microRNAs, and CYFRA-21.1, which have lower diagnostic capabilities but provide prognostic information and have potential roles as therapeutic targets. Serum is the most investigated matrix for biomarkers of PM. Several serum biomarkers in PM have been studied, with mesothelin, osteopontin, and fibulin-3 being the most often tested. A soluble mesothelin-related peptide (SMRP) is the only FDA-approved biomarker in patients with suspected mesothelioma. With different serum and pleural fluid cut-offs, it provides useful information on the diagnosis, prognosis, follow-up, and response to therapy in epithelioid PM. Panels combining different markers and proteomics technologies show promise in terms of improving clinical performance in the diagnosis and monitoring of mesothelioma patients. However, there is still no evidence that early detection can improve the treatment outcomes of PM patients.

Reducing Post-Operative Alveolo-Pleural Fistula by Applying PGA-Sheets (Neoveil) after Major Lung Resection: A Historical Case-Control Study.

Alveolo-pleural fistula remains a serious post-operative complication in lung cancer patients after surgery, which is associated with prolonged hospital stay and higher healthcare costs. The aim of this study is to evaluate the efficacy of a polyglycol acid (PGA)-sheet known as Neoveil in preventing post-operative air-leak in cases of detected intra-operative air-leak after lung resection. Between 11/2021 and 7/2022, a total of 329 non-small cell lung cancer (NSCLC) patients were surgically treated in two institutions. Major lung resections were performed in 251 cases. Among them, 44 patients with significant intra-operative air-leak at surgery were treated by reinforcing staple lines with Neoveil (study group). On the other hand, a historical group (selected by propensity score matched analysis) consisting of 44 lung cancer patients with significant intra-operative air leak treated by methods other than the application of sealant patches were considered as the control group. The presence of prolonged air-leak (primary endpoint), pleural drainage duration, hospital stay, and post-operative complication rates were evaluated. The results showed that prolonged air-leak (>5 days after surgery) was not observed in study group, while this event occurred in four patients (9.1%) in the control group. Additionally, a substantial reduction (despite not statistically significant) in the chest tube removal was noted in the study group with respect to the control group (3.5 vs. 4.5, p = 0.189). In addition, a significant decrease in hospital stay (4 vs. 6 days, p = 0.045) and a reduction in post-operative complications (2 vs. 10, p = 0.015) were observed in the study group when compared with the control group. Therefore, in cases associated with intra-operative air-leak after major lung resection, Neoveil was considered a safer and more effective aerostatic tool and represents a viable option during surgical procedures.

Optimizing the management of complicated pleural effusion: From intrapleural agents to surgery.

Pleural effusion is a frequent complication of acute pulmonary infection and can affect its morbidity and mortality. The possible evolution of a parapneumonic pleural effusion includes 3 stages: exudative (simple accumulation of pleural fluid), fibropurulent (bacterial invasion of the pleural cavity), and organized stage (scar tissue formation). Such a progression is favored by inadequate treatment or imbalance between microbial virulence and immune defenses. Biochemical features of a fibrinopurulent collection include a low pH (<7.20), low glucose level (<60 mg/dl), and high lactate dehydrogenase (LDH). A parapneumonic effusion in the fibropurulent stage is usually defined "complicated" since antibiotic therapy alone is not enough for its resolution and an invasive procedure (pleural drainage or surgery) is required. Chest ultrasound is one of the most useful imaging tests to assess the presence of a complicated pleural effusion. Simple parapneumonic effusions are usually anechoic, whereas complicated effusions often have a complex appearance (non-anechoic, loculated, or septated). When simple chest tube placement fails and/or patients are not suitable for more invasive techniques (i.e. surgery), intra-pleural instillation of fibrinolytic/enzymatic therapy (IPET) might represent a valuable treatment option to obtain the lysis of fibrin septa. IPET can be used as either initial or subsequent therapy. Further studies are ongoing or are required to help fill some gaps on the optimal management of parapneumonic pleural effusion. These include the duration of antibiotic therapy, the risk/benefit ratio of medical thoracoscopy and surgery, and new intrapleural treatments such as antibiotic-eluting chest tubes and pleural irrigation with antiseptic agents.

Does mild COPD affect prognosis in the elderly?

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects independence and survival in the general population, but it is unknown to which extent this conclusion applies to elderly people with mild disease. The aim of this study was to verify whether mild COPD, defined according to different classification systems (ATS/ERS, BTS, GOLD) impacts independence and survival in elderly (aged 65 to 74 years) or very elderly (aged 75 years or older) patients. METHODS: We used data coming from the Respiratory Health in the Elderly (Salute Respiratoria nell'Anziano, SaRA) study and compared the differences between the classification systems with regards to personal capabilities and 5-years survival, focusing on the mild stage of COPD. RESULTS: We analyzed data from 1,159 patients (49% women) with a mean age of 73.2 years (SD: 6.1). One third of participants were 75 years or older. Mild COPD, whichever was its definition, was not associated with worse personal capabilities or increased mortality after adjustment for potential confounders in both age groups. CONCLUSIONS: Mild COPD may not affect survival or personal independence of patients over 65 years of age if the reference group consists of patients with a comparable burden of non respiratory diseases. Comorbidity and age itself likely are main determinants of both outcomes.

The pleura and the endocrine system.

The functioning of the pleura and the endocrine system are not entirely independent of each other. Some hormones can reach a greater concentration in the pleural exudate than in the blood. However, the clinical significance of this finding remains unknown. In some circumstances, hormonal changes are responsible for pathological manifestations in the pleura. Hypothyroidism is one of the most common diseases that can cause a pleural effusion, likely resulting from alterations in capillary permeability. The presence of ectopic endometrial tissue within the lung parenchyma, pleura, pericardium or diaphragm is known as thoracic endometriosis and is one of the causes of catamenial pneumothorax and /or catamenial hemothorax, which can affect women of childbearing age and arises within 72 h from the onset of menstruation. Treatment and prevention of recurrent catamenial pneumothorax / hemothorax usually requires an approach that combines surgery and hormone therapy. Malignant pleural effusion from breast cancer may contain estrogen receptor-positive cells. In such a case, endocrine treatment may be effective in reducing the amount of pleural fluid and the associated symptoms. Thyroid cancer and lymphangioleiomyomatosis (LAM) are further hormone-sensitive malignancies in which pleura is frequently involved. The solitary fibrous tumor of pleura (SFPT) is an example of a pleural disease that can cause hormonal balance disorders. It can lead to a rise in the releasing factor for growth hormone (GHRH), human beta chorionic gonadotropin (Beta-hCG), and insulin-like growth factor 2 (IGF2). The consequence of such hormonal imbalance include hypertrophic pulmonary osteoarthropathy, gynecomastia, and refractory hypoglycemia, respectively.

Inhalation therapy devices for the treatment of obstructive lung diseases: the history of inhalers towards the ideal inhaler.

Inhalation therapy allows conveying drugs directly into the airways. The devices used to administer inhaled drugs play a crucial role in the management of obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). To ensure high bronchial deposition of the drug, a device should deliver a high proportion of fine particles, be easy to use, and provide constant and accurate doses of the active substance. Nowadays, four different types of inhalers are widely used: nebulizers, dry powder inhalers (DPIs), pressurized metered-dose inhalers (pMDIs), and soft mist inhalers (SMIs). Nebulizers can be used by patients unable to use other inhalers. However, they require long times of administration and do not ensure precise dosages. The first pMDIs became popular since they were small, inexpensive, fast, and silent. Their performance was improved by spacers and then by new technologies which reduced the delivery speed. In DPIs, micronized drug particles are attached to larger lactose carrier particles. No coordination between actuation and inhalation is required. However, the patient is supposed to produce an adequate inspiratory flow to extract the drug and disaggregate it from the carrier. In SMIs, the medication is dissolved in an aqueous solution, without propellant, and it is dispensed as a slow aerosol cloud thanks to the energy of a spring. Smart inhalers, connected to smartphones, are promising tools that can provide information about patient's adherence and their inhaler technique. Inhalation has also been proposed as a route of administration for several systemic drugs.

Correction to: When kidneys and lungs suffer together.

Given names of all the authors have been interchanged with family names.

When kidneys and lungs suffer together.

A significant interaction between kidneys and lungs has been shown in physiological and pathological conditions. The two organs can both be targets of the same systemic disease (eg., some vasculitides). Moreover, loss of normal function of either of them can induce direct and indirect dysregulation of the other one. Subjects suffering from COPD may have systemic inflammation, hypoxemia, endothelial dysfunction, increased sympathetic activation and increased aortic stiffness. As well as the exposure to nicotine, all the foresaid factors can induce a microvascular damage, albuminuria, and a worsening of renal function. Renal failure in COPD can be unrecognized since elderly and frail patients may have normal serum creatinine concentration. Lungs and kidneys participate in maintaining the acid-base balance. Compensatory role of the lungs rapidly expresses through an increase or reduction of ventilation. Renal compensation usually requires a few days as it is achieved through changes in bicarbonate reabsorption. Chronic kidney disease and end-stage renal diseases increase the risk of pneumonia. Vaccination against Streptococcus pneumonia and seasonal influenza is recommended for these patients. Vaccines against the last very virulent H1N1 influenza A strain are also available and effective. Acute lung injury and acute kidney injury are frequent complications in critical illnesses, associated with high morbidity and mortality. The concomitant failure of kidneys and lungs implies a multidisciplinary approach, both in terms of diagnostic processes and therapeutic management.

Asthma-COPD overlap syndrome: recent advances in diagnostic criteria and prognostic significance.

The term asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) has been proposed for individuals with features of both asthma and COPD. Several attempts have been done to define ACOS on the basis of medical history, symptoms, and functional findings. The main diagnostic criteria include airflow obstruction with a strong although incomplete reversibility to bronchodilation tests, a significant exposure to cigarette or biomass smoke, and a history of atopy or asthma. Additional diagnostic elements include eosinophilic airway and systemic inflammation, a good response to corticosteroid treatment, and a high concentration of exhaled nitric oxide. ACOS should be distinguished from asthma with not fully reversible bronchial obstruction due to airway remodeling, thus the lack of smoking exposure should exclude the diagnosis of ACOS. In patients without a documented history of asthma before 40 years of age, an increase in FEV1 after bronchodilator >400 mL should be required to diagnose ACOS. ACOS has been found to be associated with impaired physical performance, functional ability, and health-related quality of life. The prevalence of ACOS increases with aging, then it is relatively stable in elderly individuals (>65 years). Long-term mortality of subjects with ACOS is similar to COPD, and worse than asthma and healthy controls. Future research is still needed to improve the understanding and management of ACOS.

Fifteen-year mortality of patients with asthma-COPD overlap syndrome.

BACKGROUND: The coexistence of asthma and chronic obstructive pulmonary disease (asthma-COPD overlap syndrome: ACOS) is increasingly recognized but data about its prevalence and long-term mortality are needed. METHODS: Prevalence of ACOS and 15-year mortality rates were assessed in 1065 subjects aged >65years, enrolled in the SA.R.A. study, with complete clinical, lung functional and follow-up data. Physical performance, disease-related disability, and health-related quality of life (HRQL) were also evaluated. RESULTS: ACOS was found in 11.1% of subjects (29.4% of those previously diagnosed with COPD and 19.7% of those with asthma). ACOS was positively associated with impaired physical performance, functional ability, and HRQL. Individuals with ACOS had higher mortality rates than controls (7.17 per 100 person-years; mortality rate ratio: 1.83). After adjustment for the main confounders, the risk of all-cause mortality remained significantly increased in subjects with ACOS (HR: 1.82), COPD (HR: 2.12), and restriction (HR: 2.41), but not asthma. CONCLUSIONS: Long-term prognosis of ACOS was similar to COPD, and worse than asthma and healthy controls. ACOS had a significant impact on physical performance, functional ability, and HRQL.

Towards a multi-dimensional approach to COPD.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality worldwide. Clinical features of the disease include exertional dyspnea and chronic cough, while persistent airflow obstruction detected at spirometry is the defining element of the disease. Notably, subjects with smoke exposure and symptoms, but normal FEV1/FVC ratio (previously classified as "stage 0" by the GOLD classification), are not considered affected and do not require treatment according to guidelines. The recent GeneCOPD study suggested that a proportion of this population might present significant radiological features of respiratory disease. This commentary article focuses on the possible future role of chest imaging, including ultrasound of the respiratory muscles, integrated with additional functional tests, such as body plethysmography and diffusing capacity for carbon monoxide of the lungs (DLCO), in a multidimensional assessment of COPD.

Towards a multi-dimensional approach to COPD.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality worldwide. Clinical features of the disease include exertional dyspnea and chronic cough, while persistent airflow obstruction detected at spirometry is the defining element of the disease. Notably, subjects with smoke exposure and symptoms, but normal FEV1/FVC ratio (previously classified as "stage 0" by the GOLD classification), are not considered affected and do not require treatment according to guidelines. The recent GeneCOPD study suggested that a proportion of this population might present significant radiological features of respiratory disease. This commentary article focuses on the possible future role of chest imaging, including ultrasound of the respiratory muscles, integrated with additional functional tests, such as body plethysmography and diffusing capacity for carbon monoxide of the lungs (DLCO), in a multidimensional assessment of COPD.

Pharmacological Management of Elderly Patients with Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome: Room for Speculation?

Asthma and chronic obstructive pulmonary disease (COPD) are two distinct diseases that share a condition of chronic inflammation of the airways and bronchial obstruction. In clinical settings, it is not rare to come across patients who present with clinical and functional features of both diseases, posing a diagnostic dilemma. The overlap condition has been termed asthma-COPD overlap syndrome (ACOS), and mainly occurs in individuals with long-standing asthma, especially if they are also current or former smokers. Patients with ACOS have poorer health-related quality of life and a higher exacerbation rate than subjects with asthma or COPD alone. Whether ACOS is a distinct nosological entity with genetic variants or rather a condition of concomitant diseases that overlap is still a matter of debate. However, there is no doubt that extended life expectancy has increased the prevalence of asthma and COPD in older ages, and thus the probability that overlap conditions occur in clinical settings. In addition, age-associated changes of the lung create the basis for the two entities to converge on the same subject. ACOS patients may benefit from a stepwise treatment similar to that of asthma and COPD; however, the proposed therapeutic algorithms are only speculative and extrapolated from studies that are not representative of the ACOS population. Inhaled corticosteroids are the mainstay of therapy, and always in conjunction with long-acting bronchodilators. The potential heterogeneity of the overlap syndrome in terms of inflammatory features (T helper-1 vs. T helper-2 pathways) may be responsible for the different responses to treatments. The interaction between respiratory drugs and concomitant diseases should be carefully evaluated. Similarly, the effect of non-respiratory drugs, such as aspirin, statins, and ß-blockers, on lung function needs to be properly assessed.

Acute painful paraplegia in a 49-year-old man with allergic asthma.

We present a case of a 49-year-old man, with a 10-year history of bronchial asthma and nasal polyposis, who developed acutely painful paraplegia and paresthesias. Laboratory data showed elevated blood creatine kinase levels and myoglobinuria, which were diagnostic for rhabdomyolysis but only partially explained the neurological deficit. Electrophysiological studies revealed a sensorimotor neuropathy of multiple mononeuritis type. The patient also had leucocytosis with marked eosinophilia and antineutrophil cytoplasmic autoantibodies. Bronchial biopsies showed inflammatory infiltrates with a prevalence of eosinophils. All these findings led us to diagnose eosinophilic granulomatosis with polyangiitis, a systemic vasculitis with almost constant respiratory tract involvement and good response to corticosteroid treatment. This can also affect other organs including the nervous system, while muscular involvement is unusual. Some diseases deserve attention in differential diagnosis. Histology can support the diagnosis which remains essentially clinical. Steroid sparing agents/immunosuppressants are suggested for extensive disease.

Diagnosis and management of asthma in the elderly.

Bronchial asthma is one of the most common chronic diseases worldwide, and by definition not expected to recover with aging. However, the concept that asthma can affect older individuals has been largely denied in the past. In clinical practice, asthma that occurs in the most advanced ages is often diagnosed as COPD, thus leading to undertreatment or improper treatment. The heterogeneity of clinical and functional presentation of geriatric asthma, including the partial loss of reversibility and of the allergic component, contributes to this misconception. A large body of evidence has accumulated demonstrating that the prevalence of asthma in the most advanced ages is similar to that in younger ages. The frequent coexistence of comorbid conditions in older patients compared to younger asthmatics, together with age-associated changes of the human lung, may render the management of asthma a complicated task. The article addresses the main issues related to the diagnosis and treatment of asthma in the geriatric age.

Diagnosis of airway obstruction in the elderly: contribution of the SARA study.

BACKGROUND: The choice between lower limit of normal or fixed value of forced expiratory volume in one second/forced vital capacity ratio (FEV(1)/FVC) < 0.70 as the criterion for confirming airway obstruction is an open issue. In this study, we compared the criteria of lower limit of normal and fixed FEV(1)/FVC for diagnosis of airway obstruction, with a focus on healthy elderly people. METHODS: We selected 367 healthy nonsmoking subjects aged 65-93 years from 1971 participants in the population-based SARA (Salute Respiratoria nell'Anziano, Italian for "Respiratory Health in the Elderly") study, analyzed their spirometric data, and tested the relationship between spirometric indices and anthropometric variables. The lower limit of normal for FEV(1)/FVC was calculated as the fifth percentile of the normal distribution for selected subjects. RESULTS: While FEV(1) and FVC decreased significantly with aging, the relationship between FEV(1)/FVC and age was not statistically significant in men or women. The lower limit of normal for FEV(1)/FVC was 0.65 in men and 0.67 in women. Fifty-five participants (15%) had FEV(1)/FVC < 0.70 and would have been inappropriately classified as obstructed according to the Global Initiative for Obstructive Lung Disease, American Thoracic Society/European Respiratory Society, and Canadian guidelines on chronic obstructive pulmonary disease. By applying different FEV(1)/FVC thresholds for the different age groups, as previously proposed in the literature, (0.70 for <70 years, 0.65 for 70-80 years, and 0.60 for >80 years) the percentage of patients classified as obstructed decreased to 6%. No subjects older than 80 years had an FEV(1)/FVC < 0.60. CONCLUSION: The present results confirm the inadequacy of FEV(1)/FVC < 0.70 as a diagnostic criterion for airway obstruction after the age of 65 years. FEV(1)/FVC < 0.65 and <0.67 (for men and women, respectively) could identify subjects with airway obstruction in such a population. Further reduction of the threshold after 80 years is not justified.