Tracheal atypical solitary carcinoid in a so called "difficult asthma": a diagnostic challenge.

This report describes the case of a 46-year-old non-smoker housewife. She presented to our attention having a diagnosis of "difficult asthma" from another center in the previous two years. She had no allergies and had not been exposed to an excessive amount of noxious stimuli. Her chronic respiratory symptoms (dyspnea on exertion with wheezing) remained uncontrolled despite maximal anti-asthmatic inhaled therapy. An HRCT scan was performed to further investigate other pulmonary diseases that mimic asthma. It revealed a pedunculated endotracheal lesion with regular borders that obstructed 90% of the tracheal lumen. The lesion was removed via rigid bronchoscopy with laser endobronchial; histological examination revealed the presence of atypical carcinoid. Atypical carcinoids are a rare subtype of neuroendocrine lung tumor that accounts for 2% of all thoracic malignancies. They frequently arise from the central airways and cause obstructive symptoms such as coughing, wheezing, chest pain, or recurrent obstructing pneumonia, which is caused by central airway obstruction. Clinical onset is gradual and characterized by non-specific symptoms, which frequently result in misdiagnosis. As a result, in a young patient with progressive dyspnea, chronic cough, and wheezing that is not responding to anti-asthmatic treatment, second-level investigations are required and may lead to a definite diagnosis, allowing the appropriate course of treatment to begin.

The Effectiveness of Wearable Devices in Non-Communicable Diseases to Manage Physical Activity and Nutrition: Where We Are?

Wearable devices are increasingly popular in clinical and non-clinical populations as a tool for exercise prescription, monitoring of daily physical activity and nutrition, and health-related parameters management. In this regard, smart devices not only assist people in pursuing a healthier lifestyle, but also provide a constant stream of physiological and metabolic data for management of non-communicable diseases (NCDs). Although the benefits of lifestyle-based interventions (exercise and nutrition) for NCDs are well known, the potential of wearable devices to promote healthy behaviors in clinical populations is still controversial. In this narrative review, we aimed to discuss the current application of wearable devices in NCDs, highlighting their role in prescribing and monitoring daily physical activity and dietary habits in the population living with chronic diseases. None of the studies considered specifically addressed the efficacy of the use of wearable devices, and limited are those that incorporate monitoring of both physical activity and nutrition for NCDs. However, there is evidence that such devices have helped improve physical activity levels, physical fitness, body composition, and metabolic and psychological parameters. Therefore, the authors believe that the benefits obtained from the use of wearable devices are likely to translate to public health and represent one of the important tools for the development of prevention plans in everyday life and clinical practice for optimal patient management.

Effects of plyometric training on different 8-week training intensity distributions in well-trained endurance runners.

The aim of this four-armed parallel group randomized-controlled trial was to evaluate if plyometric training could have different effects on running performance and physiological adaptations depending on the training intensity distribution (TID) in an 8-week intervention in endurance athletes. Sixty well-trained male runners (age: 34 ± 6 years, relative ⩒O2peak : 69 ± 3 ml kg-1  min-1 ) were recruited and allocated to a pyramidal (PYR), pyramidal + plyometric training (PYR + PLY), polarized (POL), and polarized + plyometric training (POL + PLY) periodization. The periodization patterns were isolated manipulations of TID, while training load was kept constant. Participants were tested pre- and post-intervention for body mass, velocity at 2 and 4 mmol·L-1 of blood lactate concentration (vBLa2, vBLa4), absolute and relative ⩒O2peak and 5-km running time trial performance, counter movement jump and squat jump. There were significant group × time interactions for vBla4 (p = 0.0235), CMJ (p = 0.0234), SJ (p = 0.0168), and 5-km running time trial performance (p = 0.0035). Specifically, vBla4 and 5-km running time trial performance showed the largest post-intervention improvements in PYR + PLY (2.4% and 1.6%) and POL + PLY (2.1% and 1.8%), respectively. No significant interactions were observed for body mass, absolute and relative ⩒O2peak , peak heart rate, lactate peak and rating of perceived exertion. In conclusion, an 8-week training periodization seems to be effective in improving performance of well-trained endurance runners. Including plyometric training once a week appeared to be more efficacious in maximizing running performance improvements, independently from the TID adopted.

Differences Between Early- and Late-Onset Asthma: Role of Comorbidities in Symptom Control.

BACKGROUND: Asthma can present in early childhood or de novo in adulthood. Our understanding of the burden of comorbidities in adult asthmatic patients stratified by age at onset is incomplete. OBJECTIVES: To evaluate how different comorbidities may affect symptom control in two distinct groups of patients with early- and late-onset asthma (EOA and LOA, respectively) and to explore whether reported comorbidities are associated with lung function and inflammatory parameters. METHODS: We conducted a cross-sectional study of 175 adult asthmatic patients (aged 57.5 ± 17.1 years) recruited at our university asthma clinic. We defined EOA as asthma onset less than 12 years, and LOA as onset greater than 40 years. The primary outcome was symptom control and main comorbidities evaluated were rhinitis, gastroesophageal reflux, obesity, cardiovascular conditions, and bronchiectasis. We used multivariable regression analysis to identify potential predictors of poor control in EOA and LOA. RESULTS: Of 175 subjects, 77 had EOA (44%), 98 had LOA (56%), and comorbidities had a differential impact in the two groups. Rhinitis was more frequent in EOA (76 vs 53%; P = .02) and was associated with uncontrolled asthma (P < .001), reduced FEV1/FVC (P = .01), increased eosinophils (P = .003) and total IgE (P < .01). Conversely, in LOA, rhinitis was associated with more controlled asthma and higher FEV1/FVC (both P < .01). In EOA, only, IgE levels were directly related to blood eosinophils (r = 0.42; P <.001) and inversely to FEV1/FVC (r = -0.35; P = .002). Obesity was present in 20% of patients in both groups, but only in LOA was it associated with uncontrolled disease (P = .009), reduced FEV1/FVC (P = .009), and blood neutrophils (P = .03). In multivariable regression analysis, rhinitis in EOA and obesity in LOA were the risk factors most closely associated with poor control. Gastroesophageal reflux, cardiovascular comorbidities, and bronchiectasis did not affect control. CONCLUSIONS: Early-onset persistent asthma and late-onset asthma are distinct phenotypes with different underlying inflammatory patterns and different comorbidities affecting symptom control.

Air Pollution Exposure Impairs Airway Epithelium IFN-ß Expression in Pre-School Children.

Introduction: Air pollution is a risk factor for respiratory infections and asthma exacerbations. We previously reported impaired Type-I and Type-III interferons (IFN-ß/λ) from airway epithelial cells of preschool children with asthma and/or atopy. In this study we analyzed the association between rhinovirus-induced IFN-ß/λ epithelial expression and acute exposure to the principal outdoor air pollutants in the same cohort. Methods: We studied 34 children (17asthmatics/17non-asthmatics) undergoing fiberoptic bronchoscopy for clinical indications. Bronchial epithelial cells were harvested by brushing, cultured and experimentally infected with Rhinovirus Type 16 (RV16). RV16-induced IFN-ß and λ expression was measured by quantitative real time PCR, as was RV16vRNA. The association between IFNs and the mean exposure to PM10, SO2 and NO2 in the day preceding bronchoscopy was evaluated using a Generalized Linear Model (GLM) with Gamma distribution. Results: Acute exposure to PM10 and NO2 was negatively associated to RV16-induced IFNß mRNA. For each increase of 1ug/m3 of NO2 we found a significative decrease of 2.3x103 IFN-ß mRNA copies and for each increase of 1ug/m3 of PM10 a significative decrease of 1x103 IFN-ß mRNA copies. No significant associations were detected between IFN-λ mRNA and NO2 nor PM10. Increasing levels of NO2 (but not PM10) were found to be associated to increased RV16 replication. Conclusions: Short-term exposure to high levels of NO2 and PM10 is associated to a reduced IFN-ß expression by the airway epithelium, which may lead to increased viral replication. These findings suggest a potential mechanism underlying the link between air pollution, viral infections and asthma exacerbations.

Quantification and role of innate lymphoid cell subsets in Chronic Obstructive Pulmonary Disease.

OBJECTIVES: Innate lymphoid cells (ILCs) secrete cytokines, such as IFN-γ, IL-13 and IL-17, which are linked to chronic obstructive pulmonary disease (COPD). Here, we investigated the role of pulmonary ILCs in COPD pathogenesis. METHODS: Lung ILC subsets in COPD and control subjects were quantified using flow cytometry and associated with clinical parameters. Tissue localisation of ILC and T-cell subsets was determined by immunohistochemistry. Mice were exposed to air or cigarette smoke (CS) for 1, 4 or 24 weeks to investigate whether pulmonary ILC numbers and activation are altered and whether they contribute to CS-induced innate inflammatory responses. RESULTS: Quantification of lung ILC subsets demonstrated that ILC1 frequency in the total ILC population was elevated in COPD and was associated with smoking and severity of respiratory symptoms (COPD Assessment Test [CAT] score). All three ILC subsets localised near lymphoid aggregates in COPD. In the COPD mouse model, CS exposure in C57BL/6J mice increased ILC numbers at all time points, with relative increases in ILC1 in bronchoalveolar lavage (BAL) fluid. Importantly, CS exposure induced increases in neutrophils, monocytes and dendritic cells that remained elevated in Rag2/Il2rg-deficient mice that lack adaptive immune cells and ILCs. However, CS-induced CXCL1, IL-6, TNF-α and IFN-γ levels were reduced by ILC deficiency. CONCLUSION: The ILC1 subset is increased in COPD patients and correlates with smoking and severity of respiratory symptoms. ILCs also increase upon CS exposure in C57BL/6J mice. In the absence of adaptive immunity, ILCs contribute to CS-induced pro-inflammatory mediator release, but are redundant in CS-induced innate inflammation.

Air Pollution Relates to Airway Pathology in Children with Wheezing.

Rationale: Outdoor air pollution contributes to asthma development and exacerbations, yet its effects on airway pathology have not been defined in children. Objectives: To explore the possible link between air pollution and airway pathology, we retrospectively examined the relationship between environmental pollutants and pathological changes in bronchial biopsy specimens from children undergoing a clinically indicated bronchoscopy. Methods: Structural and inflammatory changes (basement membrane [BM] thickness, epithelial loss, eosinophils, neutrophils, macrophages, mast cells, and lymphocytes) were quantified in biopsy specimens by using immunohistochemistry. The association between exposure to particulate matter less than 10 µm in aerodynamic diameter (PM10), SO2 and NO2 and biopsy findings was evaluated by using a generalized additive model with Gamma family to allow for overdispersion, adjusted for atmospheric pressure, temperature, humidity, and wheezing. Results: Overall, 98 children were included (age 5.3 ± 2.9 yr; 53 with wheezing/45 without wheezing). BM thickness increased with prolonged exposure to PM10 (rate ratio [RR], 1.29; 95% confidence interval [CI], 1.09-1.52), particularly in children with wheezing. Prolonged exposure to PM10 was also associated with eosinophilic inflammation in children with wheezing (RR, 3.16; 95% CI, 1.35-7.39). Conversely, in children without wheezing, increased PM10 exposure was associated with a reduction of eosinophilic inflammation (RR, 0.12; 95% CI, 0.02-0.6) and neutrophilic inflammation (RR, 0.36; 95% CI, 0.14-0.89). Moreover, NO2 exposure was also linked to reductions in neutrophil infiltration (RR, 0.57; 95% CI, 0.34-0.93) and eosinophil infiltration (RR, 0.33; 95% CI, 0.14-0.77). Conclusions: Different patterns of association were observed in children with wheezing and in children without wheezing. In children without wheezing, exposure to PM10 and NO2 was linked to reduced eosinophilic and neutrophilic inflammation. Conversely, in children with wheezing, prolonged exposure to PM10 was associated with increased BM thickness and eosinophilic inflammation, suggesting that it might contribute to asthma development by promoting airway remodeling and inflammation.

The Role of Technology in Adherence to Physical Activity Programs in Patients with Chronic Diseases Experiencing Fatigue: a Systematic Review.

BACKGROUND: The beneficial role of physical activity (PA) to manage the health condition of patients with chronic diseases is well known. However, adherence to PA guidelines in this group is still low. Monitoring and user-interface technology could represent a significant tool to increase exercise adherence to those particular groups who experience difficulties in adhering to regular and substantial physical activity, and could be supportive in increasing the success of PA programs and interventions. This systematic review aimed at evaluating the effect of physical activity monitoring technology in improving adherence to a PA program in patients with chronic diseases experiencing fatigue. METHODS: This systematic review was conducted according to PRISMA guidelines. The literature search was performed in Embase, Medline, Biosis, Scopus, and SPORTDiscus. We filtered the literature according to the question: "Does monitoring technology affect adherence to physical activity and exercise programs in patients with chronic diseases perceiving fatigue?". RESULTS: The search resulted in 1790 hits; finally, eight studies were included, with a total number of 205 patients. Study quality was moderate except for one study of high quality. Only three disease types emerged, COPD, HF, and cancer. PA programs were rather short (from 8 to 13 weeks) except for one 3-year-long study. Five studies employed pedometers and two an activity monitor. Three studies based their adherence on steps, the remaining studies focused on active minutes. Adherence was explicitly reported in two studies, and otherwise derived. Four studies showed high adherence levels (85% week-10, 89% week-8, 81% week-13, 105% week-13, 83% average week-1-12) and three low levels (56% week-12, 41% year-2, 14 year-3). CONCLUSION: The small number of studies identified did not allow to establish whether the use of monitoring technology could improve adherence to PA programs in patients with chronic diseases experiencing fatigue, but the current evidence seems to suggest that this is a field warranting further study, particularly into how monitoring technology can help to engage patients to adhere to PA programs.

Clinical and Pathologic Factors Predicting Future Asthma in Wheezing Children. A Longitudinal Study.

Wheeze is a common symptom in infants, but not all wheezers develop asthma. Indeed, up to 50% of wheezing children outgrow their symptoms by school age. How to predict if early wheeze will become asthma is still a matter of vivid debate. In this work, we sought to assess the clinical and pathological factors that might predict the future development of asthma in children. Eighty children (mean age 3.8 ± 1 yr) who underwent a clinically indicated bronchoscopy were followed prospectively for a median of 5 years. At baseline, clinical characteristics with a particular focus on wheezing and its presentation (episodic or multitrigger) were collected, and structural and inflammatory changes were quantified in bronchial biopsies. Follow-up data were available for 74 of the 80 children. Children who presented with multitrigger wheeze were more likely to have asthma at follow-up than those with episodic wheeze (P = 0.04) or without wheeze (P < 0.0001). Children with asthma also had lower birth weights (P = 0.02), a lower prevalence of breastfeeding (P = 0.02), and a trend for increased IgE (P = 0.07) at baseline than those with no asthma. Basement membrane thickness and airway eosinophils at baseline were increased in children who developed asthma at follow-up (P = 0.001 and P = 0.026, respectively). Multivariate analysis showed that among all clinical and pathological factors, multitrigger wheezing, basement membrane thickening, and reduced birth weight were predictive of future asthma development. We conclude that multitrigger wheeze and reduced birth weight are clinical predictors of asthma development. Basement membrane thickening in early childhood is closely associated with asthma development, highlighting the importance of airway remodeling in early life as a risk factor for future asthma.

Anterior cruciate ligament injury profile in Italian Serie A1-A2 women's volleyball league.

BACKGROUND: The aim of this study was to assess how anterior cruciate ligament (ACL) ruptures with subsequent surgery reconstruction impact on the professional career of A1-A2 Italian women's volleyball league players. METHODS: Using an observational study with a retrospective case-series design for ACL ruptures, 125 teams with 1488 players were monitored. Subjects had to report level, role, injury modality, lower limb injured, laterality, period of the season and age. RESULTS: A total of 34 ACL ruptures were reported. Thirty-three (97%) were non-contact and 1 (3%) with contact. Twenty-one (61.7%) occurred in landing from a jump attack, 3 (8.8%) in landing from wall jump, 1 (3%) with apparent contact and 9 (26.5%) in other landing conditions. The most injured knee was the left limb (22, 64.7%) respect to the right limb (12, 35.3%). Fourteen (41.2%) ruptures occurred in spikers, 10 (29.4%) in middle blockers, 6 (17.6%) in setters, 3 (8.8%) in liberos and 1 (3%) in opposite hitters. Nine (26.5%) occurred in pre-season period, 16 (47%) in the first round, 4 (11.8%) in the second round, and 5 (14.7%) during play-off. The average age of the first ACL rupture was 23±3 years. CONCLUSIONS: We observed that female volleyball players of A1-A2 Italian volleyball league occurred mostly in a left non-contact ACL rupture during a landing condition and the spikers were the players most at risk. Therefore, it is desirable that coaches teach players variations of landing in order to avoid possible chronic overloading of ACL.

A pilot study of brisk walking in sedentary combination antiretroviral treatement (cART)- treated patients: benefit on soluble and cell inflammatory markers.

BACKGROUND: Chronic HIV infection is associated with low-level inflammation and increased risk of chronic diseases and mortality. The objective was to assess the effects of moderate intensity exercise on metabolic and inflammatory markers in HIV-infected treated persons. METHODS: This was a pilot study enrolling cART-treated, sedentary persons with metabolic complications in a 12-week protocol, consisting of three sessions per week of 60 min brisk walking with (strength-walk group) or without (walk group) 30 min circuit-training. Assessments at baseline and week 12 (W12) included body morphometrics and total body dual-energy X-ray absorptiometry; lipid and glucose blood profile; plasma level of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), D-dimer, interleukin-18 (IL-18), soluble CD14, and CD38 and HLA-DR expression on CD4+ and CD8+ T-cells. RESULTS: Forty-nine patients were included and 35 (71%) completed the program: 21 in the walk and 14 in the strength-walk group. At W12, significant improvements were observed of body mass index, waist and hip circumference, and total cholesterol both overall and in the walk group, and of LDL cholesterol in both training groups. In the whole group, significant reductions were observed in hsCRP, IL-6, D-dimer, IL-18, and of CD8+/CD38+/HLA-DR+ cell frequencies. HsCRP and CD8+/CD38+/HLA-DR+ frequency decreased significantly in both training groups when examined separately whereas IL-6 and D-dimer in the walk group only. CONCLUSIONS: Brisk walking, with or without strength exercise, could improve lipid profile and inflammatory markers in chronic HIV infection. TRIAL REGISTRATION: ACTRN12615001258549, registered 17 November 2015, "retrospectively registered" Web address of trial: http://www.ANZCTR.org.au/ACTRN12615001258549.aspx.