Hasil untuk "Diseases of the respiratory system"

Anna Lee, PhD, MPH, Derek K.W. Yau, PhD, MScMed(PainMgt), Gavin M. Joynt, MBBCh, FCICM et al.

Background: Prehabilitation enhances patients’ resilience to surgical stress and may improve postoperative outcomes. However, the dose response of prehabilitation on outcomes remains unknown. Research Question: Does a twice-weekly supervised outpatient exercise program before elective cardiac surgery in patients with frailty have dose-response effects on 90-day postoperative major cardiac and cerebrovascular events (MACCEs) and disability levels? Study Design and Methods: This was a post hoc analysis of the PREhabilitation for improving QUality of recovery after ELective cardiac surgery (PREQUEL) trial that compared physical prehabilitation (up to 19 sessions over 10 weeks) with usual care in participants with very mild to moderate frailty. Primary outcomes included the 90-day risk of MACCEs and changes in disability levels measured by the World Health Organization Disability Assessment Schedule 2.0 score. Secondary outcomes were preoperative changes in the 6-minute walk test distance, submaximal metabolic equivalents of tasks, and frailty measures. We used a generalized estimating equation model to examine the association between the dose of prehabilitation and the risk of MACCEs. Causal inference was assessed by dose-response function models while allowing nonlinearity. Results: Of the 143 participants, 135 underwent cardiac surgery. No exercise-induced adverse events occurred in 64 participants during 551 sessions. The dose of prehabilitation was not associated with the risk of MACCEs (16 participants with 24 episodes; adjusted OR/session, 0.98; 95% CI, 0.88-1.09). However, improvements in disability levels, 6-minute walk test distance, and metabolic equivalents of tasks were directly related to the number of consecutive doses of prehabilitation before surgery. Improvements in clinical frailty after exercise training were observed in a few patients after 7 weeks of training. Interpretation: In cardiac patients with frailty, a greater number of consecutive doses of physical prehabilitation had favorable effects on improving preoperative exercise capacity and lowering disability levels at 90 days after surgery. Clinical Trial Registration: Chinese Clinical Trials Registry; No.: ChiCTR1800016098; URL: https://www.chictr.org.cn/indexEN.html

Xiaoyan Yang, Hongyi Wang, Anqi Liu et al.

Abstract Objective Respiratory muscle dysfunction in patients with idiopathic pulmonary fibrosis (IPF) is a big challenge for treatment and rehabilitation. To quantitatively assess diaphragm and chest wall dysfunction using dynamic Magnetic Resonance Imaging (Dyn-MRI) in patients with IPF. Methods Ninety-six patients with IPF and 50 gender- and age-matched controls were prospectively included and underwent D-MRI with a dynamic fast spoiled gradient-recalled echo sequence. Respiratory muscles function were assessed with thoracic anterior-posterior (AP), left-right (LR), cranial-caudal (CC) metrics. Moreover, lung area ratios, height (DH), and area (DA) of diaphragm curvature between end-inspiration and end-expiration during both quiet and deep breathing. Results During quiet breathing, the functional metrics of the diaphragm and chest wall were comparable between IPF patients and controls. However, during deep breathing, IPF patients exhibited significantly reduced ratios of AP, CC, and lung area compared to controls. Moreover, the median ratios of DH and DA were higher in IPF patients than in controls (DH: 0.96 vs. 0.81, p < 0.001; DA: 1.00 vs. 0.90, p < 0.001). Furthermore, the ratios of AP, CC, and lung area during deep breathing were found to correlate with pulmonary function, total lung volume, and 6-minute walk distance. Conclusion D-MRI demonstrated dysfunction in the diaphragm and chest wall among IPF patients, with respiratory muscle dysfunction showing a correlation with the severity of disease. Trial registration This article presents a prospective observational study that does not include the outcomes of any healthcare interventions on human participants. The study was registered on September 11, 2018, under the registration number NCT03666234.

Trishul Siddharthan, Sanjay Sethi, Emily Wan et al.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a progressive disease associated with substantial morbidity and mortality. Acute COPD exacerbations are a primary driver of significant burden and contribute to disease progression. Methods This retrospective, observational cohort study used the Optum Clinformatics® Data Mart database to identify patients with COPD who were classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) A/B0 or A/B1 based on exacerbation history (i.e., they had either 0 [GOLD A/B0] or 1 [GOLD A/B1] moderate exacerbation and 0 severe exacerbations in a 12-month baseline period). Patients were required to be aged ≥ 40 years and to have newly initiated inhaled maintenance therapy for COPD from January 2016 to June 2023. The rates of and time to progression to GOLD E (defined in the claims data as experiencing 2 moderate exacerbations within a 12-month period or 1 severe exacerbation) were estimated using the Kaplain-Meier method. Predictors of progression to GOLD E were analyzed using multivariable Cox proportional hazard models. Results Of the 156,462 included patients, the largest proportion of patients (46.6%) were initiated on long-acting beta-agonists/inhaled corticosteroids. The majority of patients progressed to GOLD E over 5 years. The risk of progressing to GOLD E was approximately 3 times higher in the GOLD A/B1 versus GOLD A/B0 group (hazard ratio [HR] 2.92; 95% CI 2.84–3.00; P < 0.001). The strongest predictor of progressing to GOLD E was history of having a moderate exacerbation. Other independent predictors included older age, having Medicare versus commercial insurance, and the presence of Elixhauser comorbidities. Conclusions Despite use of inhaled maintenance treatments for COPD, most patients still progressed to a frequent or severe exacerbator phenotype. New therapies are needed to modify the disease trajectory in COPD.

Esra Hazar, Mehmet Ali Karaselek, Sevgi Keles

Gonca Koc, Aloisia Paloma Hernandez Morales, Huseyin Hudaver Alper

D. Dona’, C. Montagnani, C. di Chiara et al.

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature. Methods: Subjects under 90 days of age admitted to 35 Italian institutions for COVID-19 were included. The severity of COVID-19 was scored as mild/moderate or severe/critical following the classification reported in the literature by Venturini, Dong, Kanburoglu, and Gale. To assess the diagnostic accuracy of each classification system, we stratified all enrolled patients developing a posteriori severity score based on clinical presentation and outcomes and then compared all different scores analyzed. Results: We included 216 infants below 90 days of age. The most common symptom was fever, followed by coryza, poor feeding, cough, and gastrointestinal manifestations. According to Venturini, Dong, Kanburoglu, and Gale’s severity scores, 18%, 6%, 4.2%, and 29.6% of infants presented with severe/critical disease, respectively. A correlation analysis between these four scores and the a posteriori severity score assigned to all enrolled subjects was performed, and a crescent strength of correlation from Gale (R = 0.355, p < 0.001) to Venturini (R = 0.425, p < 0.001), Dong (R = 0.734, p < 0.001), and Kanburoglu (R = 0.859, p < 0.001) was observed. Conclusions: The percentage of infants with severe COVID-19 varies widely according to the score systems. A unique clinical score should be designed for neonates and infants with COVID-19.

S. Ornaghi, A. Maraschini, M. Buoncristiano et al.

Maternal sepsis represents a leading cause of mortality and severe morbidity worldwide. In Italy, it is the second cause of direct maternal mortality. Delay in recognition and treatment initiation are the drivers of sepsis-associated adverse outcomes. Between November 2017 and October 2019, the Italian Obstetric Surveillance System coordinated a prospective population-based study on maternal sepsis occurring before or after childbirth from 22 weeks’ gestation onward and up to 42 days following the end of pregnancy. A nested 1:2 matched case-control study on postpartum sepsis was also performed. Maternal sepsis was diagnosed for the presence of suspected or confirmed infection alongside signs or symptoms of organ failure. The aim of this study was to assess maternal sepsis incidence and its associated risk factors, management, and perinatal outcomes. Six Italian regions, covering 48.2% of the national births, participated in the project. We identified an incidence rate of 5.5 per 10,000 maternities (95% CI 4.80–6.28). Seventy percent of patients had a low education level and one third were foreigners with a language barrier. Genital, respiratory, and urinary tract infections were the predominant sources of infection; the majority of cases was caused by E. coli and polymicrobial infections. The presence of vascular and indwelling bladder catheters was associated with a nine-fold increased risk of postpartum sepsis. There were no maternal deaths, but one fourth of women experienced a serious adverse event and 28.3% required intensive care; 1.8% of newborns died. Targeted interventions to increase awareness of maternal sepsis and its risk factors and management should be promoted.

Takatora Akizawa, Tomotaka Nishizawa, Sho Yamada et al.

Epithelioid hemangioendothelioma (EHE) affects many organs, particularly lung and liver, and typically presents as multiple lesions. Treatment for EHE is not yet standardized, but surgery is appropriate when lesions are resectable. In our patient, radiography revealed multiple bilateral pulmonary nodules, and CT showed several liver tumors. The liver masses and those in the right lung were removed during the initial surgery; pathology of hepatic specimens confirmed the diagnosis of EHE. During the second operation, the left lung nodules were excised, and all were EHEs. Surgical removal of multiorgan multinodular EHE is a viable treatment option, especially for young patients.

R. D. Dal Negro, M. Carone, G. Cuttitta et al.

Background Chronic obstructive pulmonary disease (COPD) is a complex, progressive respiratory condition characterized by heterogeneous clinical presentations (phenotypes). The aim of this study was to assess the prevalence of the main COPD phenotypes and match of each phenotype to the most fitting clinical and lung function profile. Methods the CLIMA (Clinical Phenotypes in Actual Clinical Practice) study was an observational, cross-sectional investigation involving twenty-four sites evenly distributed throughout Italy. Patients were tentatively grouped based on their history and claimed prevailing symptoms at recruitment: chronic cough (CB, suggesting chronic bronchitis); dyspnoea (possible emphysema components, E); recurrent wheezing (presuming asthma components, A). Variables collected were: anagraphics; smoking habit; history of asthma; claim of >1 exacerbations in the previous year; blood eosinophil count; total blood IgE and alpha1 anti-trypsin (α1-AT) levels; complete lung function, and the chest X-ray report. mMRC, CAT, BCS, EQ5d-5L were also used. The association between variables and phenotypes were checked by Chi-square test and multinomial logistic regression. Results The CB phenotype was prevalent (48.3%), followed by the E and the A phenotypes (38.8% and 12.8%, respectively). When dyspnoea was the prevailing symptom, the probability of belonging to the COPD-E phenotype was 3.40 times higher. Recurrent wheezing was mostly related to the COPD-A phenotype. Lung function proved more preserved in the COPD-CB phenotype. Smoke; n. exacerbations/year; VR, and BODE index were positively correlated with the COPD-E phenotype, while SpO2, FEV1/FVC, FEV1/VC, and FEV1 reversibility were negatively correlated. Lower DLco values were highly probative for the COPD-E phenotype (p<0.001). Conversely, smoke, wheezing, plasma eosinophils, FEV1 reversibility, and DLco were positively correlated with the COPD-A phenotype. The probability of belonging to the COPD-A phenotype raised by 2.71 times for any increase of one unit in % plasma eosinophils (p<0.001). Also multiparametrical scores contributed to discriminate the three phenotypes. Conclusion The recognition of the main phenotypes of COPD can be effectively pursued by means of a few clinical and instrumental parameters, easy to obtain also in current daily practice. The phenotypical approach is crucial in the management of COPD as it allows to individualize the therapeutic strategy and to obtain more effective clinical outcomes.

R. Lapidot, K. Shea, I. Yildirim et al.

Background: Although a substantial decline in vaccine-serotype invasive pneumococcal disease (IPD) incidence was observed following the introduction of pneumococcal conjugate vaccines (PCV), the estimated range of thirteen-valent conjugate vaccine (PCV13) effectiveness for serotype 3 disease is wide and includes zero. We assessed the impact of PCV13 on serotype 3 IPD incidence and disease characteristics in Massachusetts’ children. Methods: Serotype 3 IPD cases in children <18 years old were identified via enhanced passive surveillance system in Massachusetts. We compared incidence rates and characteristics of IPD cases before and after PCV13. Results: A total of 47 serotype 3 IPD cases were identified from 2002 to 2017; incidence of serotype 3 IPD in the years following PCV13 was 0.19 per 100,000 children compared to 0.21 before PCV 13, incidence rate ratio (IRR) = 0.86 (95% CI 0.47–1.57). The majority (78%) of post-PCV13 serotype 3 IPD cases occurred among fully vaccinated children. Age distribution, clinical syndrome and presence of comorbidities among serotype 3 IPD cases were similar before and after PCV13 introduction. There was no association between the date of the last PCV13 dose and time to IPD to suggest waning of immunity. Conclusions: seven years following PCV 13 we found no significant changes in serotype 3 IPD incidence or disease characteristics in children in Massachusetts.

Grâce Francois, P. Cleuziou, Quentin Vannod-Michel et al.

Abstract Introduction  Various neurologic manifestations have already been described in children during or after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The central nervous system disorders reported in children are mainly encephalopathies during multisystem inflammatory syndrome. We present here an acute meningoencephalitis with cerebral vasculitis associated to a coronavirus disease 2019 (COVID-19) infection in a 13-year-old girl with a 1-year clinical, electroencephalogram (EEG), and magnetic resonance imaging (MRI) follow-up. Case Report  A 13-year-old girl presented acute symptoms of consciousness impairment, frontal headache, hyperthermia, and aphasia, with moderate lymphopenia (900/mm 3 ), elevated C-reactive protein (17 mg/L), cerebrospinal fluid (CSF) pleocytosis (15 cells/mm 3 ), slow background with frontal focalization on EEG, a left frontal ischemic lesion, leptomeningeal enhancement, and bilateral limbic fluid-attenuated inversion recovery hyperintensity on cerebral MRI. Reverse transcription-polymerase chain reaction for SARS-CoV-2 was positive in nasopharyngeal swab and COVID serology was positive for immunoglobulin (Ig) M and G, whereas extensive autoimmune antibody investigation was negative except for a positive low titer of anti-myelin oligodendrocyte glycoprotein in CSF and blood. The diagnosis of probable encephalitis associated to cerebral vasculitis after COVID infection was suggested and steroids pulse were started. She recovered within a few days. Six months later, she had moderate clinical sequels including persistent intermittent headaches, an isolated spatial deficit, and focal spikes on the EEG without argument for epilepsia. Conclusion  A teenager without previous medical history presented with acute encephalitis with leptomeningitis and vasculitis after a recent COVID-19 infection. Steroids pulse therapy allowed clinical improvement. Cerebral MRI and EEG helped diagnosis, follow-up of the encephalitis, and evolution after treatment.

Kamil Waczyński, Stefania Brejtfus, Anna Romaszko-Wojtowicz et al.

Introduction: Diseases of the respiratory system are the third cause of mortality worldwide in terms of incidence. A spirometry test enables early detection of changes in the respiratory tract of persons with minor ailments, as well as the diagnosis of a fairly advanced illness whose symptoms have been neglected by the patient. Aim: The aim of this study has been to identify any irregularities in spirometry tests in the population of the province of Warmia and Mazury. Material and methods: The study covered 1061 persons living in the province of Warmia and Mazury, of which 637 patients (188 women and 249 men) were included in the analysis. The participants provided their basic demographic and medical data through a survey. Each participant underwent a spirometry test according to the European Respiratory Society and American Thoracic Society 2005 guidelines. Statistical analysis was carried out in a Statistica software package. Results and Discussion: The study showed that women smoke significantly less than men – the average pack years for women and men were 4.02 (SD 9.33) and 8.11 (SD 17.19) (P < 0.001), respectively. A higher number of pack years contributed to a higher incidence of the respiratory tract symptoms (cough, wheeze, breathlessness) (P < 0.05). Compared to men, women were more often observed to suffer from grade 1 or 2 degree dyspnoea on the mMRC scale. Conclusions: Pulmonary function tests play an important role in the diagnosis of respiratory system diseases. Promotion of prophylactic measures in streets of cities helps to improve patients’ awareness of the condition of their health.

Mohamed Ahmed, Nahla Zaghloul, Prisca Zimmerman et al.

Pharmacologic interventions to halt/reverse the vascular remodeling and right ventricular dysfunction in pulmonary arterial hypertension (PAH) remains an unmet need. We previously demonstrated extracellular nicotinamide phosphoribosyltransferase (eNAMPT) as a DAMP (damage‐associated molecular pattern protein) contributing to PAH pathobiology via TLR4 ligation. We examined the role of endothelial cell (EC)‐specific eNAMPT in experimental PH and an eNAMPT‐neutralizing mAb as a therapeutic strategy to reverse established PH. Hemodynamic/echocardiographic measurements and tissue analyses were performed in Sprague Dawley rats exposed to 10% hypoxia/Sugen (three weeks) followed by return to normoxia and weekly intraperitoneal delivery of the eNAMPT mAb (1 mg/kg). WT C57BL/6J mice and conditional EC‐cNAMPTec−/− mice were exposed to 10% hypoxia (three weeks). Biochemical and RNA sequencing studies were performed on rat PH lung tissues and human PAH PBMCs. Hypoxia/Sugen‐exposed rats exhibited multiple indices of severe PH (right ventricular systolic pressure, Fulton index), including severe vascular remodeling, compared to control rats. PH severity indices and plasma levels of eNAMPT, IL‐6, and TNF‐α were all significantly attenuated by eNAMPT mAb neutralization. Compared to hypoxia‐exposed WT mice, cNAMPTec−/− KO mice exhibited significantly reduced PH severity and evidence of EC to mesenchymal transition (EndMT). Finally, biochemical and RNAseq analyses revealed eNAMPT mAb‐mediated rectification of dysregulated inflammatory signaling pathways (TLR/NF‐κB, MAP kinase, Akt/mTOR) and EndMT in rat PH lung tissues and human PAH PBMCs. These studies underscore EC‐derived eNAMPT as a key contributor to PAH pathobiology and support the eNAMPT/TLR4 inflammatory pathway as a highly druggable therapeutic target to reduce PH severity and reverse PAH.

J.C. Winck, R. Scala

COVID-19 related Acute Respiratory Failure, may be successfully treated with Conventional Oxygen therapy, High Flow Nasal Cannula, Continuous Positive Airway Pressure or Bi-level Positive-Pressure ventilation. Despite the accumulated data in favor of the use of different Non-invasive Respiratory therapies in COVID-19 related Acute Respiratory Failure, it is not fully understood when start, escalate and de-escalate the best respiratory supportive option for the different timing of the disease. Based on the current published experience with Non-invasive Respiratory therapies in COVID-19 related Acute Respiratory Failure, we propose an algorithm in deciding when to start, when to stop and when to wean different NIRT. This strategy may help clinicians in better choosing NIRT during this second COVID-19 wave and beyond.

D. Loconsole, M. Giordano, F. Centrone et al.

Shiga toxin-producing Escherichia coli (STEC) infections result in a significant public health impact because of the severity of the disease that, in young children especially, can lead to hemolytic–uremic syndrome (HUS). A rise in the number of HUS cases was observed in the Apulia region of Italy from 2013 to 2017, and so, in 2018, a symptom-based surveillance system for children with bloody diarrhea (BD) was initiated in order to detect and manage STEC infections. The objective of the study was to describe the epidemiology of STEC infections in children from June 2018 to August 2019. Children <15 years old with BD were hospitalized and tested for STEC. Real-time PCR for virulence genes (stx1, stx2, eae) and serogroup identification tests were performed on stool samples/rectal swabs of cases. STEC infection was detected in 87 (10.6%) BD cases. The median age of STEC cases was 2.7 years, and 60 (68.9%) were <4. Of these 87 cases, 12 (13.8%) came from households with diarrhea. The reporting rate was 14.2/100,000, with the highest incidence in cases from the province of Bari (24.2/100,000). Serogroups O26 and O111 were both detected in 22/87 (25.3%) cases. Co-infections occurred in 12.6% of cases (11/87). Twenty-nine STEC were positive for stx1, stx2, and eae. Five cases (5.7%) caused by O26 (n = 2), O111 (n = 2), and O45 (n = 1) developed into HUS. A risk-oriented approach based on the testing of children with BD during the summer may represent a potentially beneficial option to improve the sensitivity of STEC surveillance, not only in Italy but also in the context of Europe as a whole.

T. C. Tran, T. A. Ngo, T. Nguyen et al.

The COVID-19 (coronavirus disease-2019) pandemic has affected almost all countries in the world. When the first cases were reported from Hubei, China, in late December 2019, the Vietnamese authorities acknowledged the potential risk of an epidemic having had the experience of severe acute respiratory syndrome (SARS) and the Avian flu. When it was clear that there was human-to-human transmission in the epidemic in Wuhan that started in January 2020, the Vietnamese government, health care system, and civil society were rapidly mobilized. How has a country with a population of about 100 million and a long porous border to China managed to prevent a larger outbreak? This case history is about how Hai Phong city implemented the initial COVID-19 response. Hai Phong reacted quickly after the COVID-19 outbreak in China by, quarantining people coming from pandemic areas, and carrying out contact tracing and extensive testing, closing schools and universities and implementing two weeks of social distancing measures. There are no detected positive cases until May 18, 2020 in Hai Phong.

Garcia IFF, Tiuganji CT, Simões MSMP et al.

Isabel Fialho Fontenele Garcia,1 Carina Tiemi Tiuganji,1 Maria do Socorro Morais Pereira Sim&otilde;es,2 Adriana Claudia Lunardi1,3 1Master&rsquo;s and Doctoral, Programs in Physical Therapy, Universidade Cidade de S&atilde;o Paulo, S&atilde;o Paulo, SP, Brazil; 2Department of Human Movement Sciences, Universidade Federal de S&atilde;o Paulo, Santos, SP, Brazil; 3Department of Physical Therapy, School of Medicine, Universidade de S&atilde;o Paulo, S&atilde;o Paulo, SP, BrazilCorrespondence: Adriana Claudia LunardiMaster&rsquo;s and Doctoral Programs in Physical Therapy, Universidade Cidade de S&atilde;o Paulo, 448/475 Ces&aacute;rio Galeno Street, S&atilde;o Paulo 03071-000, SP, BrazilTel +55 11 2178-1310Fax +55 11 2178-1355Email adriana.lunardi@unicid.edu.brPurpose: The aim of this study was to investigate whether limitation during the performance of activities of daily living (ADL) was associated with life-space mobility in older people with chronic obstructive pulmonary disease (COPD), and to generate a regression model for life-space mobility score.Patients and Methods: This cross-sectional study with a convenience sample included older people (aged &ge;60 years old) with COPD. We assessed participants&rsquo; lung function (spirometry), life-space mobility (University of Alabama at Birmingham Study of Aging Life-Space Assessment questionnaire), severity of dyspnea (Modified Dyspnea Index) and limitation during the performance of ADL (London Chest Activity of Daily Living). We used Pearson&rsquo;s correlation to investigate the associations between the measures, and multiple linear regression to detect which of the measures influenced life-space mobility. Statistical significance was set at 5%.Results: Fifty participants completed all the assessments (29 females [58%]; mean &plusmn; SD age of 67 &plusmn; 6 years old, FEV1 47 &plusmn; 29% of predicted, and body mass index 22.5 &plusmn; 11.6 kg/m2). Their mean scores for life-space mobility and for limitation during the performance of ADL were 49.7 &plusmn; 27.2 and 16.46 &plusmn; 9.74, respectively. We found a strong inverse correlation between limitation during the performance of ADL and life-space mobility (r = &minus;0.57, p = &lt;0.01) as well as between severity of dyspnea and life-space mobility (r= 0.86, p= &lt;0.01). Both sex and limitation during the performance of ADL were considered as independent factors associated to life-space mobility (R2= 0.56).Conclusion: In this study, limitations during the performance of ADL and dyspnea had a strong correlation with life-space mobility in older adults with COPD. Also, alongside sex, the limitation during the performance of ADL is an independent factor associated with life-space mobility in a regression model.Keywords: COPD, older adult, mobility limitation, activities of daily living

Miguel J. Divo, Michael R. DePietro, John R. Horton et al.

Abstract Background Studies suggest that acute decreases in lung hyperinflation at rest improves cardiac function and increases lung vascular perfusion from decompression of a compromised heart. In those studies, changes in resting oxygen uptake induced by medications, an alternative explanation for compensatory increased cardiac function, were not explored. Methods This double-blind, multicenter, double-crossover study enrolled adults with chronic obstructive pulmonary disease, resting hyperinflation, and > 10% improvement in inspiratory capacity after 2 inhalations of budesonide/formoterol 160/4.5 μg. Metabolic, cardiac, and ventilatory function were measured 60 min pre−/post-dose at each visit. Primary endpoint was change in resting oxygen uptake for budesonide/formoterol versus placebo. Results Fifty-one patients (median age: 63 years) received treatment. Compared with placebo, budesonide/formoterol significantly increased resting oxygen uptake (mean change from baseline: 1.25 vs 11.37 mL/min; P = 0.007) as well as tidal volume and minute ventilation. This occurred despite improvements in the inspiratory capacity, forced vital capacity, and expiratory volume in 1 s. No significant treatment differences were seen for oxygen saturation, respiratory rate, and resting dyspnea. There was a numerical increase in oxygen pulse (oxygen uptake/heart rate). Correlations between inspiratory capacity and oxygen pulse were weak. Conclusions Budesonide/formoterol treatment in resting hyperinflated patients with COPD results in significant deflation. The increase in oxygen uptake and minute ventilation at lower lung volumes, without changes in heart rate and with minimal improvement in oxygen pulse, suggests increased oxygen demand as a contributor to increased cardiac function. Trial registration ClinicalTrials.gov identifier: NCT02533505.

Matsuo Y, Ogawa E, Seto-Yukimura R et al.

Yumiko Matsuo,1 Emiko Ogawa,1,2 Ruriko Seto-Yukimura,1 Yasushi Ryujin,1,3 Daisuke Kinose,1 Masafumi Yamaguchi,1 Makoto Osawa,1 Taishi Nagao,1 Hajime Kurosawa,4 Yasutaka Nakano1 1Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science, Shiga, Japan; 2Health Administration Center, Shiga University of Medical Science, Shiga, Japan; 3Ryujin Medical Clinic, Osaka, Japan; 4Center for Environmental Conservation and Research Safety, Department of Occupation Health, Tohoku University, Miyagi, JapanCorrespondence: Emiko OgawaHealth Administration Center, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga 520-2192, JapanTel/Fax +81-77-548-2212Email eogawa@belle.shiga-med.ac.jpPurpose: The forced oscillation technique (FOT) is a non-invasive method to measure respiratory impedance, the respiratory resistance (Rrs) and reactance (Xrs). The disease probability measure (DPM) is a useful computed tomography (CT) imaging variable for the assessment of gas trapping and emphysema in patients with chronic obstructive pulmonary disease (COPD) using pairs of inspiratory and expiratory CT images. We aimed to develop FOT-based phenotypes and determine whether the phenotypes and their imaging characteristics could facilitate the understanding of COPD pathophysiology.Patients and methods: FOT and spirometry were examined in 164 COPD patients and 22 non-COPD smokers. COPD patients were divided into four FOT-based phenotypes (NL, normal group; RD, resistance-dominant group; XD, reactance-dominant group; and MIX, mixed group) based on the 3rd quartile values of R5 (Rrs at 5Hz) and X5 (Xrs at 5Hz) in the non-COPD group. The emphysematous lesions and the airway lesions were quantitatively assessed in CT images by low attenuation volume and the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (&radic;Aaw at Pi10), respectively. DPM imaging analysis was also performed in 131 COPD patients. We investigated the differences in COPD parameters between the FOT-based phenotypes.Results: &radic;Aaw at Pi10 were significantly higher in the RD, XD, and MIX groups than in the NL group. The XD group showed lower pulmonary function and higher dyspnea scores than the RD group. No significant changes in DPM values were observed between the RD and the NL groups. The gas-trapping area was significantly higher in the XD group than in the NL group. The MIX group showed the highest dyspnea score, most emphysematous lesions, and the lowest forced expiratory volume in 1 s % predicted value.Conclusion: The FOT-based phenotyping may be useful to assess pathophysiological changes of COPD with CT assessments.Keywords: oscillometry, emphysema, exhalation, quantitative evaluation, COPD

Steven J. Pascoe, Alberto Papi, Dawn Midwinter et al.

Abstract Background Patients with chronic obstructive pulmonary disease (COPD) have excess risk of developing pneumonia; however, no definitive biomarkers of risk have been established. We hypothesized that blood neutrophils would help predict pneumonia risk in COPD. Methods A meta-analysis of randomized, double-blind clinical trials of COPD patients meeting the following criteria were selected from the GlaxoSmithKline trial registry: ≥1 inhaled corticosteroid-containing (ICS) arm (fluticasone propionate/salmeterol or fluticasone furoate/vilanterol), a control arm (non-ICS), pre-randomization blood neutrophil counts, ≥24-week duration. The number of patients with pneumonia events and time to first event (Kaplan–Meier analysis) were evaluated (post-hoc), stratified by baseline blood neutrophil count and ICS use. A Cox proportional hazards model was used to calculate hazard ratios (HR), split by median baseline blood neutrophils. Results Ten studies (1998 to 2011) with 11,131 patients were identified. The ICS (n = 6735) and non-ICS (n = 4396) cohorts were well matched in neutrophil distributions and demographics. Increasing neutrophil count was associated with an increased proportion of patients with pneumonia events; patients below the median neutrophil count were at less risk of a pneumonia event (HR, 0.75 [95% confidence interval 0.61–0.92]), and had longer time to a first event, compared with those at/above the median. The increase in pneumonia risk by neutrophil count was similar between the two cohorts. Conclusions Increased blood neutrophils in COPD were associated with increased pneumonia risk, independent of ICS use. These data suggest blood neutrophils may be a useful marker in defining treatment pathways in COPD.