The utility of serial procalcitonin measurements in addition to pneumonia severity scores in hospitalised community-acquired pneumonia: A multicentre, prospective study.

OBJECTIVES: The usefulness of serial procalcitonin (PCT) measurements for predicting the prognosis and treatment efficacy for hospitalised community-acquired pneumonia (CAP) patients was investigated. METHODS: This prospective, multicentre, cohort study enrolled consecutive CAP patients who were hospitalised at 10 hospitals in western Japan from September 2013 to September 2016. PCT and C-reactive protein (CRP) were measured on admission (PCT D1 and CRP D1), within 48-72 h after admission (PCT D3 and CRP D3), and within 144-192 h after admission. CURB-65 and the Pneumonia Severity Index (PSI) were assessed on admission. The primary outcome was 30-day mortality; secondary outcomes were early and late treatment failure rates. RESULTS: A total of 710 patients were included. The 30-day mortality rate was 3.1%. On multivariate analysis, only PCT D3/D1 ratio >1 [odds ratio (95% confidence interval): 4.33 (1.46-12.82),P = 0.008] and PSI [odds ratio (95% confidence interval): 2.32 (1.07-5.03), P = 0.03] were significant prognostic factors. Regarding treatment efficacy, PCT D3/D1 >1 was a significant predictor of early treatment failure on multivariate analysis. PCT D3/D1 with the PSI significantly improved the prognostic accuracy over that of the PSI alone. CONCLUSIONS: PCT should be measured consecutively, not only on admission, to predict the prognosis and treatment efficacy in CAP.

Radiographic Evidence of Sinonasal Inflammation in Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome: An Underrecognized Association.

BACKGROUND: Sinonasal inflammation on both clinical examinations and imaging significantly impacts both asthma and chronic obstructive pulmonary disease (COPD). OBJECTIVE: The objective of this study was to examine the association between sinonasal inflammation and asthma-COPD overlap syndrome (ACOS). METHODS: A total of 112 patients with a ratio of forced expiratory volume in 1 s to forced vital capacity of less than 70% were enrolled. COPD, asthma, and ACOS were clinically diagnosed according to the 2014 Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease guidelines. Sinonasal inflammatory condition was evaluated using sinus computed tomography, and its severity was assessed according to the Lund-Mackay staging (LMS) system. Ethmoid sinus-dominant shadow was defined as the presence of greater LMS scores for the anterior and posterior ethmoid sinuses than for the maxillary sinus. RESULTS: COPD, asthma, and ACOS were diagnosed in 55 (49.1%), 39 (34.8%), and 18 patients (16.1%), respectively. The frequency of radiographic evidence of sinonasal inflammation in patients with COPD, asthma, ACOS was 60.0%, 94.9%, and 72.2%, respectively. Patients with ACOS and COPD had only mild radiographic evidence of sinonasal inflammation (LMS score, 1-7), whereas moderate (LMS score, 8-11) and severe (LMS score, ≥12) radiographic evidence of sinonasal inflammation were detected only in patients with asthma. Furthermore, the frequency of ethmoid sinus-dominant shadow was significantly higher in patients with asthma than in those with COPD and ACOS. CONCLUSIONS: Radiographic evidence of sinonasal inflammation was a common comorbidity in ACOS. Future studies are required to examine the role of sinonasal inflammation in ACOS.

Nasal nitric oxide improved by continuous positive airway pressure therapy for upper airway inflammation in obstructive sleep apnea.

PURPOSE: In this report, we examined the association between obstructive sleep apnea (OSA) and upper and lower airway inflammation based on nitric oxide (NO) measurements. METHODS: Study subjects included 51 consecutive participants. Sleep-disordered breathing was evaluated by a type 3 portable monitor and quantified by respiratory disturbance index (RDI). Airway inflammation was noninvasively analyzed by the measurement of nasally and orally exhaled NO; nasal value was presented as nasally exhaled NO minus orally exhaled NO. In 15 patients prescribed nasal continuous positive airway pressure (nCPAP) therapy, exhaled NO was re-evaluated in 10.7 ± 6.3 months after nCPAP therapy. RESULTS: Nasal NO was significantly higher in patients with severe OSA (RDI ≥ 30/h) than those with non-OSA (RDI < 10/h) (76.9 ± 26.0 ppb vs. 47.9 ± 22.0 ppb, respectively, p = 0.016) and correlated with RDI (rho = 0.36, p = 0.0099), whereas orally exhaled NO did not differ between non-OSA and OSA patients and was not correlated with RDI. In 15 patients, nasal NO after nCPAP therapy was significantly decreased than that before nCPAP therapy (81.9 ± 31.2 ppb vs. 53.7 ± 27.2 ppb, respectively, p = 0.0046); in 11 patients having good compliance to nCPAP therapy (nCPAP use >4 h per night on more than 70% of nights), this association was more remarkable. CONCLUSIONS: In OSA, upper but not lower airway inflammation can be increased by repetitive collapse of the upper airway. Future studies are required to determine the role of nasal NO in OSA.

Environmental risk factors for pulmonary Mycobacterium avium-intracellulare complex disease.

BACKGROUND: Mycobacterium avium-intracellulare complex (MAC) is a ubiquitous pathogen found in soil and water. Environmental exposure is the primary route for MAC infection. However, specific environmental risk factors have been poorly determined in immunocompetent patients with pulmonary MAC disease. METHODS: A case-control study was performed with 106 patients with pulmonary MAC disease (men [women], 23 [83]; age, 64.3 ± 9.2 years) and 53 age-matched control patients with bronchiectasis but not pulmonary MAC infection (men [women], 7[46]; age, 63.0 ± 11.0 years). All participants completed a standardized questionnaire that included questions about medical history, smoking history, alcohol usage, age at menopause, and environment exposures. Environment exposures included soil exposure from farming or gardening; water exposure from bathing, showering, hot tub use, dishwashing, swimming, and drinking water; and pet exposure. RESULTS: No differences were identified in the patient characteristics and underlying diseases. More case patients experienced high soil exposure (≥ 2 per week) than control patients (23.6% vs 9.4%, P = .032); this remained significant after multivariate analysis (OR, 5.9; 95% CI, 1.4-24.7; P = .015). There were no significant differences in other environmental exposures. Case patients with high soil exposure were significantly older than those with low soil exposure (67.3 ± 7.3 years vs 64.3 ± 9.5 years, P = .037). Other characteristics, underlying diseases, and mycobacterial species did not differ between the two groups. CONCLUSIONS: Patients with pulmonary MAC disease had significantly more soil exposure than noninfected control patients, which suggests that environmental soil exposure is a likely risk factor for the development of pulmonary MAC disease.

Ionic mechanisms of cardiac cell swelling induced by blocking Na+/K+ pump as revealed by experiments and simulation.

Although the Na(+)/K(+) pump is one of the key mechanisms responsible for maintaining cell volume, we have observed experimentally that cell volume remained almost constant during 90 min exposure of guinea pig ventricular myocytes to ouabain. Simulation of this finding using a comprehensive cardiac cell model (Kyoto model incorporating Cl(-) and water fluxes) predicted roles for the plasma membrane Ca(2+)-ATPase (PMCA) and Na(+)/Ca(2+) exchanger, in addition to low membrane permeabilities for Na(+) and Cl(-), in maintaining cell volume. PMCA might help maintain the [Ca(2+)] gradient across the membrane though compromised, and thereby promote reverse Na(+)/Ca(2+) exchange stimulated by the increased [Na(+)](i) as well as the membrane depolarization. Na(+) extrusion via Na(+)/Ca(2+) exchange delayed cell swelling during Na(+)/K(+) pump block. Supporting these model predictions, we observed ventricular cell swelling after blocking Na(+)/Ca(2+) exchange with KB-R7943 or SEA0400 in the presence of ouabain. When Cl(-) conductance via the cystic fibrosis transmembrane conductance regulator (CFTR) was activated with isoproterenol during the ouabain treatment, cells showed an initial shrinkage to 94.2 +/- 0.5%, followed by a marked swelling 52.0 +/- 4.9 min after drug application. Concomitantly with the onset of swelling, a rapid jump of membrane potential was observed. These experimental observations could be reproduced well by the model simulations. Namely, the Cl(-) efflux via CFTR accompanied by a concomitant cation efflux caused the initial volume decrease. Then, the gradual membrane depolarization induced by the Na(+)/K(+) pump block activated the window current of the L-type Ca(2+) current, which increased [Ca(2+)](i). Finally, the activation of Ca(2+)-dependent cation conductance induced the jump of membrane potential, and the rapid accumulation of intracellular Na(+) accompanied by the Cl(-) influx via CFTR, resulting in the cell swelling. The pivotal role of L-type Ca(2+) channels predicted in the simulation was demonstrated in experiments, where blocking Ca(2+) channels resulted in a much delayed cell swelling.