Identifying vagal bronchopulmonary afferents mediating cough response to inhaled sulfur dioxide in mice.

Sulfur dioxide (SO2), a common environmental and industrial air pollutant, possesses a potent effect in eliciting cough reflex, but the primary type of airway sensory receptors involved in its tussive action has not been clearly identified. This study was carried out to determine the relative roles of three major types of vagal bronchopulmonary afferents [slowly adapting receptors (SARs), rapidly adapting receptors (RARs), and C-fibers] in regulating the cough response to inhaled SO2. Our results showed that inhalation of SO2 (300 or 600 ppm for 8 min) evoked an abrupt and intense stimulatory effect on bronchopulmonary C-fibers, which continued for the entire duration of inhalation challenge and returned toward the baseline in 1-2 min after resuming room air-breathing in anesthetized and mechanically ventilated mice. In stark contrast, the same SO2 inhalation challenge generated a distinct and consistent inhibitory effect on both SARs and phasic RARs; their phasic discharges synchronized with respiratory cycles during the baseline (breathing room air) began to decline progressively within 1-3 min after the onset of SO2 inhalation, ceased completely before termination of the 8-min inhalation challenge, and then slowly returned toward the baseline after >40 min. In a parallel study in awake mice, inhalation of SO2 at the same concentration and duration as that in the nerve recording experiments evoked cough responses in a pattern and time course similar to that observed in the C-fiber responses. Based on these results, we concluded that stimulation of vagal bronchopulmonary C-fibers is primarily responsible for triggering the cough response to inhaled SO2.NEW & NOTEWORTHY This study demonstrated that inhalation of a high concentration of sulfur dioxide, an irritant gas and common air pollutant, completely and reversibly inhibited the neural activities of both slowly adapting receptor and rapidly adapting receptor, two major types of mechanoreceptors in the lungs with their activities conducted by myelinated fibers. Furthermore, the results of this study suggested that stimulation of vagal bronchopulmonary C-fibers is primarily responsible for triggering the cough reflex responses to inhaled sulfur dioxide.

Incidence risk assessment of secondary cancer due to radiotherapy of women with rectal cancer using BEIR VII, EPA, and ICRP models.

Background: Radiotherapy has a significant side effect known as radiation-induced secondary cancer. This study aims to evaluate the dose and secondary cancer risk for women with rectal cancer treated with three-dimensional conformal radiation therapy (3D-CRT) to the organs at risk (OARs) and some sensitive organs using different types of radiation-induced cancer risk prediction models, including Biological Effects of Ionizing Radiation (BEIRVII), Environmental Protection Agency (EPA) and International Commission on Radiological Protection (ICRP), and compare the results of the different models for same organs. Materials and methods: Thirty female patients with rectal cancer were considered and dose calculations were based on the PCRT-3D treatment planning system, while the radiotherapy of the patients had been performed using Shinva linear accelerator with a total dose of 45 Gy at 25 fractions. Planning target volume (PTV), OARs, and some sensitive organs were contoured, three models were used to evaluate secondary cancer risk (SCR) using the excess relative risk (ERR) and excess absolute risk (EAR). Results: The bladder presents the highest risk, in terms of ERR, and the femur head and uterus in terms of EAR from the three models (BEIR VII, EPA, and ICRP). Conclusion: Based on the obtained results, radiotherapy of rectal cancer is relatively higher for the bladder and femur head, compared to the risk for other organs, the kidney risk is significantly lower. It was observed that the SCR from the ICRP model was higher compared to BEIR VII and EPA models.

Trends and progress in application of cobalt-based materials in catalytic, electrocatalytic, photocatalytic, and photoelectrocatalytic water splitting.

There has been a growing interest in water oxidation in recent two decades. Along with that, remarkable discovery of formation of a mysterious catalyst layer upon application of an anodic potential of 1.13 V vs. standard hydrogen electrode (SHE) to an inert indium tin oxide electrode immersed in phosphate buffer containing Co(II) ions by Nocera et.al, has greatly attracted researchers interest. These researches have oriented in two directions; one focuses on obtaining better understanding of the reported mysterious catalyst layer, further modification, and improved performance, and the second approach is about designing coordination complexes of cobalt and investigating their properties toward the application in water splitting. Although there have been critical debates on true catalysts that are responsible for water oxidation in homogeneous systems of coordination complexes of cobalt, and the case is not totally closed, in this short review, our focus will be mainly on recent major progress and developments in the design and the application of cobalt oxide-based materials in catalytic, electrocatalytic, photocatalytic, and photoelectrocatalytic water oxidation reaction, which have been reported since pioneering report of Nocera in 2008 (Kanan Matthew and Nocera Daniel in Science 321:1072-1075, 2008).

Increased IL-6 and Potential IL-6 trans-signalling in the airways after an allergen challenge.

BACKGROUND: In asthma, IL-6 is a potential cause of enhanced inflammation, tissue damage and airway dysfunction. IL-6 signalling is regulated by its receptor, which is composed of two proteins, IL-6R and GP130. In addition to their membrane form, these two proteins may be found as extracellular soluble forms. The interaction of IL-6 with soluble IL-6R (sIL-6R) can trigger IL-6 trans-signalling in cells lacking IL-6R. Conversely, the soluble form of GP130 (sGP130) competes with its membrane form to inhibit IL-6 trans-signalling. OBJECTIVES: We aimed to analyse IL-6 trans-signalling proteins in the airways of subjects after an allergen challenge. METHODS: We used a model of segmental bronchoprovocation with an allergen (SBP-Ag) in human subjects with allergy. Before and 48 h after SBP-Ag, bronchoalveolar lavages (BALs) allowed for the analysis of proteins in BAL fluids (BALFs) by ELISA, and membrane proteins on the surface of BAL cells by flow cytometry. In addition, we performed RNA sequencing (RNA-seq) and used proteomic data to further inform on the expression of the IL-6R subunits by eosinophils, bronchial epithelial cells and lung fibroblasts. Finally, we measured the effect of IL-6 trans-signalling on bronchial fibroblasts, in vitro. RESULTS: IL-6, sIL-6R, sGP130 and the molar ratio of sIL-6R/sGP130 increased in the airways after SBP-Ag, suggesting the potential for enhanced IL-6 trans-signalling activity. BAL lymphocytes, monocytes and eosinophils displayed IL-6R on their surface and were all possible providers of sIL-6R, whereas GP130 was highly expressed in bronchial epithelial cells and lung fibroblasts. Finally, bronchial fibroblasts activated by IL-6 trans-signalling produced enhanced amounts of the chemokine, MCP-1 (CCL2). CONCLUSION AND CLINICAL RELEVANCE: After a bronchial allergen challenge, we found augmentation of the elements of IL-6 trans-signalling. Allergen-induced IL-6 trans-signalling activity can activate fibroblasts to produce chemokines that can further enhance inflammation and lung dysfunction.

Airway hypersensitivity induced by eosinophil granule-derived cationic proteins.

Vagal bronchopulmonary C-fiber sensory nerves play an important role in the manifestation of airway hypersensitivity, a common and prominent pathophysiological feature of airway inflammatory diseases. Eosinophil granule-derived cationic proteins are known to be involved in the mucosal damage and development of bronchial hyperresponsiveness during allergic airway inflammation. In view of these background information, we have carried out a series of studies to investigate the effect of cationic proteins on these C-fiber afferents and the mechanism(s) possibly involved; a summary of these studies is presented in this mini-review. Intra-tracheal instillation of either eosinophil granule-derived (e.g., major basic protein, MBP) or synthetic cationic proteins (e.g., poly-l-lysine) induced a sporadic, but intense and lingering discharge of pulmonary C-fibers, and greatly enhanced the chemical and mechanical sensitivities of these afferents in anesthetized rats. The stimulatory and sensitizing effects of these proteins were completely nullified when their cationic charges were neutralized or removed. Furthermore, in isolated rat bronchopulmonary capsaicin-sensitive neurons, eosinophil granule cationic proteins induced a direct and long-lasting (>60 min) but reversible sensitizing effect on their responses to chemical and electrical stimulations. More importantly, our study showed that these cationic proteins exerted an inhibitory effect on the sustained delayed-rectifier voltage-gated K+ current and the A-type, fast-inactivating K+ current; these actions were at least in part responsible for the sensitizing effect in these neurons. In awake mice, intra-tracheal instillation of MBP also induced a slowly developing (peaking in 2-3 days), progressive and sustained (lasting for 3-7 days) elevation of the cough responses to inhaled irritant gases. Taken together, these findings suggest that the enhanced sensitivity of bronchopulmonary C-fibers induced by the eosinophil granule cationic proteins may be a contributing factor in the pathogenesis of bronchial hyperresponsiveness and chronic cough associated with eosinophilic infiltration of the airways.

Cough and expiration reflexes elicited by inhaled irritant gases are intensified in ovalbumin-sensitized mice.

This study was designed to determine the effect of active sensitization with ovalbumin (Ova) on cough responses to inhaled irritant gases in mice. Conscious mice moved freely in a recording chamber, while the pressure change in the chamber and audio and video signals of the mouse movements were recorded simultaneously to measure the frequencies of cough reflex (CR) and expiration reflex (ER). To further verify the accuracy of cough analysis, the intrapleural pressure was also recorded by a telemetry sensor surgically implanted in the intrapleural space in a subgroup of mice. During the irritant gas inhalation challenge, sulfur dioxide (SO2; 200 and 400 ppm) or ammonia (NH3; 0.1% and 0.2%) was drawn into the chamber at a constant flow rate for 8 min. Ova sensitization and sham sensitization with vehicle (Veh) were performed over a 25-day period in separate groups of mice. Our results showed that 1) both SO2 and NH3 inhalation challenges increased CR and ER frequencies in a concentration-dependent manner before Ova sensitization; 2) the baseline CR frequency was significantly elevated after Ova sensitization, accompanied by pronounced airway inflammation; and 3) Ova sensitization also markedly augmented the responses of CR and ER to both SO2 and NH3 inhalation challenges; in sharp contrast, the cough responses did not change after sham sensitization in the Veh group. In conclusion, Ova sensitization caused distinct and lingering increases in baseline cough frequency, and also intensified both CR and ER responses to inhaled irritant gases, which probably resulted from an allergic inflammation-induced hypersensitivity of airway sensory nerves.

Sustained sensitizing effects of tumor necrosis factor alpha on sensory nerves in lung and airways.

Tumor necrosis factor alpha (TNFα) plays a significant role in the pathogenesis of airway inflammatory diseases. Inhalation of aerosolized TNFα induced airway hyperresponsiveness accompanied by airway inflammation in healthy human subjects, but the underlying mechanism is not fully understood. We recently reported a series of studies aimed to investigate if TNFα elevates the sensitivity of vagal bronchopulmonary sensory nerves in a mouse model; these studies are summarized in this mini-review. Our results showed that intratracheal instillation of TNFα induced pronounced airway inflammation 24 h later, as illustrated by infiltration of eosinophils and neutrophils and the release of inflammatory mediators and cytokines in the lung and airways. Accompanying these inflammatory reactions, the sensitivity of vagal pulmonary C-fibers and silent rapidly adapting receptors to capsaicin, a selective agonist of transient receptor potential vanilloid type 1 receptor, was markedly elevated after the TNFα treatment. A distinct increase in the sensitivity to capsaicin induced by TNFα was also observed in isolated pulmonary sensory neurons, suggesting that the sensitizing effect is mediated primarily through a direct action of TNFα on these neurons. Furthermore, the same TNFα treatment also induced a lingering (>7days) cough hyperresponsiveness to inhalation challenge of NH3 in awake mice. Both the airway inflammation and the sensitizing effect on pulmonary sensory neurons caused by the TNFα treatment were abolished in the TNF-receptor double homozygous mutant mice, indicating the involvement of TNF-receptor activation. These findings suggest that the TNFα-induced hypersensitivity of vagal bronchopulmonary afferents may be responsible for, at least in part, the airway hyperresponsiveness caused by inhaled TNFα in healthy individuals.

Analysis of the Normal Electrocardiogram in Wild Rooks ( Corvus frugilegus ).

To describe the normal electrocardiographic (ECG) patterns and values in unanesthetized rooks ( Corvus frugilegus ), standard bipolar (I, II, and III) and augmented unipolar limb (aVR, aVL, and aVF) lead ECGs were recorded from 10 clinically healthy wild rooks. Wave forms were analyzed in all leads at 50 mm/s and at 10 mm = 1 mV to determine PR, QRS, ST, and QT durations; the net QRS complex; and P and T amplitudes. The polarity of each waveform was tabulated in all leads. The mean electrical axis (MEA) for the frontal plane was counted by using leads II and III. The mean heart rate was 340 ± 18 beats/min. The P wave was mainly positive in the most leads. The dominant pattern of waveforms of the QRS complexes was QS in leads II, III, and aVF, whereas in leads aVR and aVL, the patterns were rS and R, respectively. The T wave was positive in leads II, III, aVF, and aVL and negative in lead aVR. The mean of the heart MEA was -93 ± 2.2. Interpretation of the ECG values and patterns in rooks may facilitate a better realization of ECG changes of abnormalities in this species.

Hypersensitivity of vagal pulmonary C-fibers induced by increasing airway temperature in ovalbumin-sensitized rats.

Our recent study has shown that hyperventilation of humidified warm air (HWA) triggered cough and reflex bronchoconstriction in patients with mild asthma. We suggested that a sensitizing effect on bronchopulmonary C-fibers by increasing airway temperature was involved, but direct evidence was lacking. This study was carried out to test the hypothesis that HWA enhances the pulmonary C-fiber sensitivity in Brown-Norway rats sensitized with ovalbumin (Ova). In anesthetized rats, isocapnic hyperventilation of HWA for 3 min rapidly elevated airway temperature to a steady state of 41.7°C. Immediately after the HWA challenge, the baseline fiber activity (FA) of pulmonary C-fibers was markedly elevated in sensitized rats, but not in control rats. Furthermore, the response of pulmonary C-fibers to right atrial injection of capsaicin in sensitized rats was significantly higher than control rats before the HWA challenge, and the response to capsaicin was further amplified after HWA in sensitized rats (ΔFA = 4.51 ± 1.02 imp/s before, and 9.26 ± 1.74 imp/s after the HWA challenge). A similar pattern of the HWA-induced potentiation of the FA response to phenylbiguanide, another chemical stimulant of C-fibers, was also found in sensitized rats. These results clearly demonstrated that increasing airway temperature significantly elevated both the baseline activity and responses to chemical stimuli of pulmonary C-fibers in Ova-sensitized rats. In conclusion, this study supports the hypothesis that the increased excitability of these afferents may have contributed to the cough and reflex bronchoconstriction evoked by hyperventilation of HWA in patients with asthma.

Interaction between TRPA1 and TRPV1: Synergy on pulmonary sensory nerves.

Transient receptor potential ankyrin type 1 (TRPA1) and vanilloid type 1 (TRPV1) receptors are co-expressed in vagal pulmonary C-fiber sensory nerves. Because both these ligand-gated non-selective cation channels are sensitive to a number of endogenous inflammatory mediators, it is highly probable that they can be activated simultaneously during airway inflammation. Studies were carried out to investigate whether there is an interaction between these two polymodal transducers upon simultaneous activation, and how it modulates the activity of vagal pulmonary C-fiber sensory nerves. Our studies showed a distinct potentiating effect induced abruptly by simultaneous activations of TRPA1 and TRPV1 by their respective selective agonists, allyl isothiocyanate (AITC) and capsaicin (Cap), at near-threshold concentrations. This synergistic effect was demonstrated in the studies of single-unit recording of vagal bronchopulmonary C-fiber afferents and the reflex responses elicited by activation of these afferents in intact animals, as well as in the isolated nodose and jugular bronchopulmonary sensory neurons. This potentiating effect was absent when either AITC or Cap was replaced by non-TRPA1 and non-TRPV1 chemical activators of these neurons, demonstrating the selectivity of the interaction between these two TRP channels. Furthermore, the synergism was dependent upon the extracellular Ca(2+), and the rapid onset of the action further suggests that the interaction probably occurred locally at the sites of these channels. These findings suggest that the TRPA1-TRPV1 interaction may play an important role in regulating the function and excitability of pulmonary sensory neurons during airway inflammation, but the mechanism underlying this positive interaction is not yet fully understood.

Release of ATP in the Lung Evoked by Inhalation of Irritant Gases in Rats.

Adenosine triphosphate (ATP) can be released into the extracellular milieu from various types of cells in response to a wide range of physical or chemical stresses. In the respiratory tract, extracellular ATP is recognized as an important signal molecule and trigger of airway inflammation. Chlorine (Cl2), sulfur dioxide (SO2), and ammonia (NH3) are potent irritant gases and common industrial air pollutants due to their widespread uses as chemical agents. This study was carried out to determine if acute inhalation challenges of these irritant gases, at the concentration and duration simulating the accidental exposures to these chemical gases in industrial operations, triggered the release of ATP in the rat respiratory tract; and if so, whether the level of ATP in bronchoalveolar lavage fluid (BALF) evoked by inhalation challenge of a given irritant gas was elevated by chronic allergic airway inflammation. Our results showed: 1) Inhalation of these irritant gases caused significant increases in the ATP level in BALF, and the magnitude of evoked ATP release was in the order of Cl2 > SO2 > NH3. 2) Chronic airway inflammation induced by ovalbumin-sensitization markedly elevated the ATP level in BALF during baseline (breathing room air) but did not potentiate the release of ATP in the lung triggered by inhalation challenges of these irritant gases. These findings suggested a possible involvement of the ATP release in the lung in the regulation of overall airway responses to acute inhalation of irritant gases and the pathogenesis of chronic allergic airway inflammation.

Enhanced generation of suppressor T cells in patients with asthma taking oral contraceptives.

Introduction. A dysregulation of regulatory T cells (Tregs) could play a major role in the pathogenesis of bronchial asthma. Sex-dependent differences as well as the impact of hormonal changes in the incidence and severity of asthma are widely recognized. Emerging evidence suggests that asthma symptoms are alleviated in female patients taking hormone oral contraceptives (OCs). The impact of OCs on the generation of induced Tregs (iTregs) was assessed in a cohort of female patients with asthma. Methods. Thirteen patients were included in this pilot study. During three distinct phases of their menstrual cycles, we measured exhaled nitric oxide (eNO) levels, forced expiratory volume at 1 second (FEV1s), asthma control test (ACT) score, sex steroid hormone levels in serum, natural Tregs in peripheral blood, and the ability of CD4(+) T cells to generate iTregs ex vivo. Results. The luteal serum levels of estradiol and progesterone negatively correlated with the proportion of iTregs generated ex vivo in patients not taking OCs. In addition, physiological doses of estradiol and progesterone prevented the acquisition of a suppressor T cell phenotype in vitro. Interestingly, patients taking OCs had reduced serum sex hormone levels associated with higher iTreg induction, a better ACT score, and a tendency toward lower eNO levels. Conclusions. Our results identify an impact of sex hormones on the capacity of T cells to polarize towards a regulatory phenotype and suggest the regulation of peripheral T cell lineage plasticity as a potential mechanism underlying the beneficial effects of OCs in women with asthma.

Bronchoconstriction triggered by breathing hot humid air in patients with asthma: role of cholinergic reflex.

RATIONALE: Hyperventilation of hot humid air induces transient bronchoconstriction in patients with asthma; the underlying mechanism is not known. Recent studies showed that an increase in temperature activates vagal bronchopulmonary C-fiber sensory nerves, which upon activation can elicit reflex bronchoconstriction. OBJECTIVES: This study was designed to test the hypothesis that the bronchoconstriction induced by increasing airway temperature in patients with asthma is mediated through cholinergic reflex resulting from activation of these airway sensory nerves. METHODS: Specific airway resistance (SR(aw)) and pulmonary function were measured to determine the airway responses to isocapnic hyperventilation of humidified air at hot (49°C; HA) and room temperature (20-22°C; RA) for 4 minutes in six patients with mild asthma and six healthy subjects. A double-blind design was used to compare the effects between pretreatments with ipratropium bromide and placebo aerosols on the airway responses to HA challenge in these patients. MEASUREMENTS AND MAIN RESULTS: SR(aw) increased by 112% immediately after hyperventilation of HA and by only 38% after RA in patients with asthma. Breathing HA, but not RA, triggered coughs in these patients. In contrast, hyperventilation of HA did not cause cough and increased SR(aw) by only 22% in healthy subjects; there was no difference between their SR(aw) responses to HA and RA challenges. More importantly, pretreatment with ipratropium completely prevented the HA-induced bronchoconstriction in patients with asthma. CONCLUSIONS: Bronchoconstriction induced by increasing airway temperature in patients with asthma is mediated through the cholinergic reflex pathway. The concomitant increase in cough response further indicates an involvement of airway sensory nerves, presumably the thermosensitive C-fiber afferents.

Comparative clinical outcomes of using three-dimensional and TIGR mesh in immediate breast reconstruction surgery for breast cancer patients.

INTRODUCTION: Breast reconstruction (BR) surgery is a widely utilized approach for women who have undergone mastectomy. Using synthetic mesh can offer advantages over other materials providing long-lasting support and natural-looking results. This study aims to compare the effectiveness of 3DMax™ mesh to TIGR mesh in BR surgery, providing clear information about the non-inferiority of 3DMax™ mesh to TIGR. METHODS: This retrospective cohort study evaluates postoperative complications in breast cancer patients who underwent subcutaneous mastectomy with direct-to-implant immediate BR using silicone implants and either 3DMax™ mesh or TIGR® Matrix Surgical Mesh. RESULTS: This study involved BR surgeries in 82 patients, including 57 surgeries in the 3D mesh group and 49 in the TIGR mesh group. The two groups had no significant differences regarding age, body mass index (BMI), cancer stage, or surgical complications. However, patients with neoadjuvant chemotherapy or radiotherapy had higher incidence rates of long-term complications than other patients. Patients with infection or partial necrosis had a heightened risk of implant loss. CONCLUSION: The clinical results obtained in this study suggest that among synthetic meshes used in immediate BR, 3DMax™ is not inferior to TIGR Matrix Surgical Mesh regarding complications.

Lung transplantation in patients with coal workers' pneumoconiosis.

Patients with coal workers' pneumoconiosis (CWP) can develop chronic respiratory failure and require lung transplantation. A retrospective review was performed of the 712 referrals and 143 patients undergoing unilateral or bilateral lung transplantation at the University of Kentucky Medical Center between January 1999 and July 2009. Twenty-one of the 712 referrals (3%) had a diagnosis of CWP with eight patients eventually undergoing lung transplant (six single, two bilateral). The mean age of the cohort was 53 ± 5 (mean ± SD) yr (range 45-59). There was no increased risk of perioperative or postoperative complications. Six patients (75%) remain alive after a mean follow-up of 1013 ± 857 d with the two deaths attributable to sepsis 683 and 145 d after transplant, respectively. There were no pulmonary complications because of the native lung in patients after a single lung transplant, with otherwise good clinical outcomes seen after lung transplantation.

Assessment of Field-in-Field, 3-Field, and 4-Field Treatment Planning Methods for Radiotherapy of Gastro-Esophageal Junction Cancer.

Background: Gastro-esophageal (GE) junction cancer is the fastest-growing tumor, particularly in the United States (US). Objective: This study aimed to compare dosimetric and radiobiological factors among field-in-field (FIF), three-field (3F), and four-field box (4FB) radiotherapy planning techniques for gastro-esophageal junction cancer. Material and Methods: In this experimental study, thirty patients with GE junction cancer were evaluated, and three planning techniques (field-in-field (FIF), three-field (3F), and four-field box (4FB)) were performed for each patient for a 6-MV photon beam. Dose distribution in the target volume, the monitor units (MUs) required, and the dose delivered to organs at risk (OARs) were compared for these techniques using the paired-sample t-test. Results: A significant difference was measured between the FIF and 3F techniques with respect to conformity index (CI), dose homogeneity index (HI), and tumor control probability (TCP) for the target organ, as well as the Dmean for the heart, kidneys, and liver. For the spinal cord, the FIF technique showed a slight reduction in the maximum dose compared to the other two techniques. In addition, the V20 Gy of the lungs and the normal tissue complication probability (NTCP) of all OARs were reduced with FIF method. Conclusion: The FIF technique showed better performance for treating patients with gastro-esophageal junction tumors, in terms of dose homogeneity in the target, conformity of the radiation field with the target volume, TCP, less dose to healthy organs, and fewer MU.

Asthma, chronic obstructive pulmonary disease, and mortality in the U.S. population.

BACKGROUND: COPD and asthma are common diseases in the U.S. population and can coexist. Our goal was to determine the prevalence of self-reported, physician-diagnosed asthma and COPD in a sample of the U.S. population and their association with lung function impairment and mortality. METHODS: We used baseline data from NHANES III and the follow-up mortality data. We used logistic regression and Cox Proportional Hazards models, adjusting for age, sex, race/ethnicity, education level, smoking status, and disease stage. RESULTS: The sample consisted of 15,203 subjects, of whom 4,542 died during the follow-up period. Coexisting COPD and asthma was reported by 357 (2.7%), COPD by 815 (5.3%), and asthma by 709 (5.3%). Subjects with both conditions had a higher proportion of obstruction (30.9%) than those with COPD (24.3%), asthma (13.3%), or no lung disease (5.4%). In survival models adjusting for all factors except baseline lung function, coexisting COPD and asthma had the highest risk for mortality (Hazard Ratio [HR] 1.83, 95% confidence interval [CI] 1.34, 2.49), followed by COPD only (HR 1.44, 95% CI 1.28, 1.62), and asthma only (HR 1.16, 95% CI 0.94, 1.42). These affects were attenuated after controlling for baseline lung function: coexisting asthma and COPD (HR 1.45, 95% CI 1.06, 1.98), COPD only (1.28, 95% CI 1.13, 1.45), and asthma only (HR 1.04, 95% CI 0.85, 1.27). CONCLUSION: In this analysis, subjects who report coexisting asthma and COPD have a higher risk of obstruction on spirometry and a higher risk of death during follow-up.

A Distinct Difference Between Air and Mucosal Temperatures in Human Respiratory Tract.

Extensive evidence indicates that several types of temperature-sensitive ion channels are abundantly expressed in the sensory nerves innervating airway mucosa. Indeed, airway temperature is known to play an important role in regulating respiratory functions. However, the actual airway mucosal temperature and its dynamic changes during the respiratory cycle have not been directly measured. In previous studies, airway tissue temperature was often estimated by indirect measurement of the peak exhaled breath temperature (PEBT). In view of the poor thermal conductivity of air, we believe that the airway tissue temperature cannot be accurately determined by the exhaled air temperature, and this study aimed to test this hypothesis. We applied a miniature rapid-response temperature probe to measure directly the mucosal temperatures of trachea, major, lobar, and segmental bronchi in eight human subjects during a bronchoscopy procedure. Unlike the air temperature in the airway lumen, the mucosal temperature in these airway segments remained relatively stable and did not exhibit the phasic changes synchronous with respiratory cycles. The airway mucosal temperature increased progressively from the extra-thoracic trachea (35.7 ± 0.2°C) toward the segmental bronchus (36.9 ± 0.2°C). Most importantly, the temperatures measured directly at the mucosa of all these airway segments were substantially higher than the PEBT (31.7 ± 0.8°C). The recent findings of a close association between an increased PEBT and airway tissue inflammation have revealed the implication and potential of incorporating the PEBT measurement in the future clinical diagnosis of airway inflammation. Therefore, it is imperative to recognize this distinct difference in temperature between airway mucosa and exhaled air.

Clever COVID-19, Clever Citizens-98: Critical and Creative Reflections from Tehran, Toronto, and Sydney.

Our world suffers. Some people suffer more than others. Since the first part of 2020, ours is justly described as a time of uncertainty, threat, and upheaval. In this article, we offer reflections threaded narratively, told from the specificity of our societal contexts in Iran, Canada, and Australia. What might we learn in the present and anticipated future from people living chronically within conditions of uncertainty and immobility and also those experiencing uncertainty and immobility for the first time? We argue that reflexive comparative analysis bridging social and visual analysis, anchored in embodied conditions of such people, offers a way to learn from responses to COVID-19 while also being an exercise in ethical research practice. This reflection builds on and extends from our scholarly collaborations that have been ongoing since 2015. Our title recognizes this specific virus as stealthy. Importantly, our choice of words identifies resident Iranians-whose experiences were the original impetuses for this paper, and whose lives provide its empirical basis (98 is Iran's country code)-as equally steely.

A continuous fluorescence assay for the determination of calcium-dependent secretory phospholipase A2 activity in serum.

BACKGROUND: Calcium-dependent secretory phospholipase A(2)-IIA (sPLA(2)-IIA) in the circulation is a marker of inflammation, associated with acute and chronic disease processes. We describe a quick, sensitive and reliable microplate continuous fluorescence assay for determining sPLA(2) activity in serum. METHODS: Liposomes composed of a fluorescent probe and varying amounts of L-alpha-phosphatidylglycerol (PG) and 1,2-dioleoyl-L-alpha-phosphatidylcholine (DOPC) were used as substrates to determine the optimal protocol for sPLA(2) activity determination without interference from serum albumin and lipoproteins. RESULTS: Hydrolysis of the labeled substrate by sPLA(2)-IIA, characterized by increase in fluorescence intensity (FI) and confirmed by end-product analysis, occurred in a time-, calcium-, and protein-dependent manner. Liposomes containing 100% PG were most suitable for measurement of sPLA(2) activity without interference from serum components; LDL produced a Ca(2+)-independent increase in FI when liposomes containing DOPC were used. The assay determined that sPLA(2) activity in serum spiked with sPLA(2)-IIA and illustrated that endogenous sPLA(2) activity was markedly higher in sera from patients with sepsis than in healthy subjects. Intra-assay and inter-assay CVs were in the ranges of 1.6-8.8% and 3.0-11.5%, respectively. CONCLUSIONS: The described method has potential for rapid and sensitive screening of sPLA(2) activity in both clinical and research settings.