The effect of 50% oxygen on PtCO2 in patients with stable COPD, bronchiectasis, and neuromuscular disease or kyphoscoliosis: randomised cross-over trials.

BACKGROUND: High-concentration oxygen therapy causes increased arterial partial pressure of carbon dioxide (PaCO2) in patients with COPD, asthma, pneumonia, obesity and acute lung injury. The objective of these studies was to investigate whether this physiological response to oxygen therapy occurs in stable patients with neuromuscular disease or kyphoscoliosis, and bronchiectasis. METHODS: Three randomised cross-over trials recruited stable patients with neuromuscular disease or kyphoscoliosis (n = 20), bronchiectasis (n = 24), and COPD (n = 24). Participants were randomised to receive 50% oxygen and 21% oxygen (air), each for 30 min, in randomly assigned order. The primary outcome was transcutaneous partial pressure of carbon dioxide (PtCO2) at 30 min. The primary analysis was a mixed linear model. RESULTS: Sixty six of the 68 participants had baseline PtCO2 values < 45 mmHg. The intervention baseline adjusted PtCO2 difference (95% CI) between oxygen and room air after 30 min was 0.2 mmHg (- 0.4 to 0.9), P = 0.40; 0.5 mmHg (- 0.2 to 1.2), P = 0.18; and 1.3 mmHg (0.7 to 1.8), P < 0.001, in the neuromuscular/kyphoscoliosis, bronchiectasis and COPD participants respectively. CONCLUSIONS: The small increase in PtCO2 in the stable COPD patients with high-concentration oxygen therapy contrasts with the marked increases in PaCO2 seen in the setting of acute exacerbations of COPD. This suggests that the model of studying the effects of high-concentration oxygen therapy in patients with stable respiratory disease is not generalisable to the use of oxygen therapy in the acute clinical setting. Appropriate studies of high-concentration compared to titrated oxygen in acute clinical settings are needed to determine if there is a risk of oxygen-induced hypercapnia in patients with neuromuscular disease, kyphoscoliosis or bronchiectasis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000970549 Registered 16/9/15, ACTRN12615000971538 Registered 16/9/15 and ACTRN12615001056583 Registered 7/10/15.

Gonadal and Endocrine Analysis of a Gynandromorphic Chicken.

Birds have a ZZ male and ZW female sex chromosome system. The relative roles of genetics and hormones in regulating avian sexual development have been revealed by studies on gynandromorphs. Gynandromorphs are rare bilateral sex chimeras, male on one side of the body and female on the other. We examined a naturally occurring gynandromorphic chicken that was externally male on the right side of the body and female on the left. The bird was diploid but with a mix of ZZ and ZW cells that correlated with the asymmetric sexual phenotype. The male side was 96% ZZ, and the female side was 77% ZZ and 23% ZW. The gonads of this bird at sexual maturity were largely testicular. The right gonad was a testis, with SOX9+ Sertoli cells, DMRT1+ germ cells, and active spermatogenesis. The left gonad was primarily testicular, but with some peripheral aromatase-expressing follicles. The bird had low levels of serum estradiol and high levels of testosterone, as expected for a male. Despite the low percentage of ZW cells on that side, the left side had female sex-linked feathering, smaller muscle mass, smaller leg and spur, and smaller wattle than the male side. This indicates that these sexually dimorphic structures must be at least partly independent of sex steroid effects. Even a small percentage of ZW cells appears sufficient to support female sexual differentiation. Given the lack of chromosome-wide dosage compensation in birds, various sexually dimorphic features may arise due to Z-gene dosage differences between the sexes.

Physiological effects of titrated oxygen via nasal high-flow cannulae in COPD exacerbations: A randomized controlled cross-over trial.

BACKGROUND AND OBJECTIVE: Increased arterial carbon dioxide tension (PaCO2 ) is an important complication of acute exacerbations of COPD. The effects of nasal high-flow cannulae (NHF) on PaCO2 in patients with COPD exacerbations, and whether this therapy should be used in this clinical situation, are less certain. We aimed to investigate the effect of NHF on PaCO2 in patients admitted to hospital with a COPD exacerbation. METHODS: We performed a single-centre randomized controlled cross-over trial in 24 hospital inpatients with acute exacerbations of COPD receiving oxygen via standard nasal prongs (SNPs). Patients received both supplemental oxygen via NHF (35 L/min) and SNP for 30 min each, with oxygen titrated to maintain the patient's baseline oxygen saturation, measured by pulse oximetry (SpO2 ). Interventions were administered in random order with a minimum 15-min washout between interventions. The primary outcome was difference in transcutaneous carbon dioxide tension (PtCO2 ) at 30 min adjusted for time zero. RESULTS: The difference in PtCO2 adjusted for time zero was lower after 30 min for NHF compared with SNP (-1.4 mm Hg (95% CI: -2.2 to -0.6), P = 0.001). There was no difference in SpO2 at 30 min (-0.02% (95% CI: -0.8 to 0.7), P = 0.96). The reduction in respiratory rate for NHF at 30 min was not statistically significant (-2.0 breaths/min (95% CI: -4.5 to 0.4), P = 0.099). CONCLUSION: Short-term use of NHF results in a small reduction in PtCO2 compared with SNP in patients with acute exacerbations of COPD, but whether this is clinically significant is uncertain.

Tolerability of Nasal Delivery of Humidified and Warmed Air at Different Temperatures: A Randomised Double-Blind Pilot Study.

OBJECTIVES: Delivery of warmed, humidified air via nasal high flow therapy could potentially reduce replication of temperature-sensitive viruses in the upper respiratory tract. This study investigates whether nasal high flow therapy is well tolerated by healthy adults at 37°C and 41°C. METHODS: In this randomised, double-blind, controlled crossover pilot trial, nasal high flow therapy was used to deliver humidified air at 35 L/min, at either 37°C or 41°C, for three one-hour sessions of use over one day. The alternative was delivered at least 14 days later. Ten healthy, nonsmoking adults were asked, via questionnaire after each day's use, whether they would use nasal high flow therapy while being unwell with a cold or flu if it was demonstrated to improve symptoms. RESULTS: All participants completed both interventions. Eighty percent responded "yes" to future use of nasal high flow therapy, for both 37°C and 41°C. There was no significant change from baseline in saccharin times following either intervention or in the following morning. CONCLUSIONS: Delivering humidified air via nasal high flow therapy at both 37°C and 41°C is well tolerated by healthy adults. This supports investigation into the potential use of nasal high flow therapy as treatment in viral upper respiratory tract infections. Trial Registration. This trial is registered with ACTRN12614000183684 (tolerability study of nasal delivery of humidified & warmed air).

Hospital admissions for non-cystic fibrosis bronchiectasis in New Zealand.

AIM: To investigate hospital admissions for non-cystic fibrosis bronchiectasis during July 1, 2008 to June 30, 2013; and to describe their distribution and annual cost in New Zealand. METHODS: Admissions with a principal diagnosis of bronchiectasis (ICD10 J47), excluding cystic fibrosis, and length of stay <90 days were analysed by age, sex, ethnicity, socioeconomic deprivation, DHB, re-admissions and seasonality. RESULTS: There were 5,494 admissions with a mean annual rate of 25.7 (age adjusted rate 20.4) per 100,000. Admission rates peaked in childhood and in the elderly, and increased steeply with socioeconomic deprivation. Age-adjusted rates were 38% higher for women, 4.9-fold higher for Maori and 9.1-fold higher for Pacific peoples. Counties Manukau had the highest unadjusted rate for any DHB (49.4 per 100,000). The overall 30 day readmission rate was 12.4%. Admissions peaked in winter and spring. The estimated cost in financial year 2012/13 was NZD 5.34M. CONCLUSION: Hospital admissions for bronchiectasis are concentrated in socioeconomically disadvantaged young and elderly Maori and Pacific peoples; are more common in winter and spring, and incur a high annual cost. Evidence-based interventions to reduce the disproportionate burden of bronchiectasis in Maori and Pacific children and the elderly is a public health priority.

Mycotic keratitis due to Scedosporium apiospermum in layer pullets.

Investigation of ocular disease in a flock of layer pullets identified corneal infection with Scedosporium apiospermum, a fungus of emerging significance in medicine and veterinary medicine.

Antineutrophil cytoplasmic autoantibodies and myeloperoxidase autoantibodies in clinical expression of Churg-Strauss syndrome.

BACKGROUND: The clinical significance of antineutrophil cytoplasmic antibodies (ANCAs) in the phenotypic expression of Churg-Strauss syndrome (CSS) is uncertain. OBJECTIVE: We sought to investigate the relationship between ANCA status and the clinical expression of CSS in a case series derived from the US Food and Drug Administration's adverse events database. METHODS: All cases of CSS reported to the US Food and Drug Administration from 1997 to April 2003 were reviewed. Information about basic demographics, suspect medication use, clinical manifestations, histologic findings, ANCA staining patterns, and the presence of antibodies to myeloperoxidase (anti-MPO) or proteinase 3 (anti-PR3) was recorded when available. RESULTS: There were 93 case reports of CSS with sufficient documentation, including ANCA status. There were 38 (40.9%) of 93 cases with positive ANCA results, of which 15 cases reported a positive ELISA, all of which were positive for anti-MPO. ANCA negativity was associated with an increased proportion of cardiac involvement (risk difference [RD], 38.2%; 95% CI, 25.3% to 51.0%), gastrointestinal involvement (RD, 25.5%; 95% CI, 13.9% to 37.0%), pulmonary infiltrates (odds ratio, 4.9; 95% CI, 1.5-16.2), and the outcome of a life-threatening event or death (RD, 30.9%; 95% CI, 18.7% to 43.1%) when compared with anti-MPO-positive cases. ANCA negativity was associated with a decreased proportion of peripheral neuropathy (odds ratio, 0.3; 95% CI, 0.07-0.9). CONCLUSION: These findings support the hypothesis that the presence or absence of autoantibodies influences the clinical expression and severity of CSS.

Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma.

BACKGROUND: The effect on Paco2 of high concentration oxygen therapy when administered to patients with severe exacerbations of asthma is uncertain. METHODS: 106 patients with severe exacerbations of asthma presenting to the Emergency Department were randomised to high concentration oxygen (8 l/min via medium concentration mask) or titrated oxygen (to achieve oxygen saturations between 93% and 95%) for 60 min. Patients with chronic obstructive pulmonary disease or disorders associated with hypercapnic respiratory failure were excluded. The transcutaneous partial pressure of carbon dioxide (Ptco2) was measured at 0, 20, 40 and 60 min. The primary outcome variable was the proportion of patients with a rise in Ptco2 ≥4 mm Hg at 60 min. RESULTS: The proportion of patients with a rise in Ptco2 ≥4 mm Hg at 60 min was significantly higher in the high concentration oxygen group, 22/50 (44%) vs. 10/53 (19%), RR 2.3 (95% CI 1.2 to 4.4, p<0.006). The high concentration group had a higher proportion of patients with a rise in Ptco2 ≥8 mm Hg, 11/50 (22%) vs. 3/53 (6%), RR 3.9 (95% CI 1.2 to 13.1, p=0.016). All 10 patients with a final Ptco2 ≥45 mm Hg received high concentration oxygen therapy, and in five there was an increase in Ptco2 ≥10 mm Hg. CONCLUSION: High concentration oxygen therapy causes a clinically significant increase in Ptco2 in patients presenting with severe exacerbations of asthma. A titrated oxygen regime is recommended in the treatment of severe asthma, in which oxygen is administered only to patients with hypoxaemia, in a dose that relieves hypoxaemia without causing hyperoxaemia. Clinical trial number ACTRN12607000131459.

Communication and health protection issues arising from a flooding emergency.

OBJECTIVE: To identify and describe the key communication and health protection issues surrounding a flooding emergency. METHODS: A telephone questionnaire was used to assess health and safety information sources, information recalled, and behavioral responses among residents of the town of Feilding, New Zealand following a major flood in February 2004. This was supplemented by key informant interviews and a newspaper content analysis. RESULTS: A total of 154 adult residents were surveyed (76% of those successfully contacted and eligible). Of the respondents, 79% recalled being provided with health and safety information from authorities. The major sources were: radio (41%), pamphlets (23%), and newspapers (20%). The regional newspaper had extensive coverage of this flooding emergency but "health" only was mentioned in 46 (7%) of the 664 flood-related articles. Of those who recalled receiving information from authorities, most (89%) perceived that it was adequate. Nevertheless, 18% actively sought out information (mainly about water safety and availability). In the post-flood period, 73% of all respondents boiled water; however, only 4% maintained boiling water or bottled water use for the necessary nine-week period. Some forms of emergency preparations did not change substantially from before the flood, compared to four months afterwards (e.g., having a radio with batteries increased from 62% to 68%). Perceived health concerns around the flooding were low, though 59% were concerned about the risk of water contamination. Actual self-reported, health consequences from the flood were rare, as only two (1%) people out of 154 reported flood-related health problems. CONCLUSIONS: Health and safety information generally was communicated successfully and was regarded as appropriate by the population of this flood-affected town. Nevertheless, there are further improvements needed in the emergency response by both residents and authorities.

Metabolism of the intervertebral disc: effects of low levels of oxygen, glucose, and pH on rates of energy metabolism of bovine nucleus pulposus cells.

STUDY DESIGN: In vitro measurements of metabolic rates of isolated bovine nucleus pulposus cells at varying levels of oxygen, glucose, and pH. OBJECTIVES: To obtain quantitative information on the interactions between oxygen and glucose concentrations and pH, and the rates of oxygen and glucose consumption and lactic acid production, for disc nucleus cells. SUMMARY OF BACKGROUND DATA: Disc cells depend on diffusion from blood vessels at the disc margins for supply of nutrients. Loss of supply is thought to lead to disc degeneration, but how loss of supply affects nutrient concentrations in the disc is not known; nutrient concentrations within discs can normally only be calculated, because concentration measurements are invasive. However, realistic predictions cannot be made until there are data from measurements of metabolic rates at conditions found in the disc in vivo, i.e., at low levels of oxygen, glucose, and pH. METHODS: A metabolism chamber was designed to allow simultaneous recording of oxygen and glucose concentrations and of pH. These concentrations were measured electrochemically with custom-built glucose and oxygen sensors; lactic acid was measured biochemically. Bovine nucleus pulposus cells were isolated and inserted into the chamber, and simultaneous rates of oxygen and glucose consumption and of lactic acid production were measured over a range of glucose, oxygen, and pH levels. RESULTS: There were strong interactions between rates of metabolism and oxygen consumption and pH. At atmospheric oxygen levels, oxygen consumption rate at pH 6.2 was 32% of that at pH 7.4. The rate fell by 60% as oxygen concentration was decreased from 21 to 5% at pH 7.4, but only by 20% at pH 6.2. Similar interactions were seen for lactic acid production and glucose consumption rates; we found that glycolysis rates fell at low oxygen and glucose concentrations and low pH. Equations were derived that satisfactorily predict the effect of nutrient and metabolite concentrations on rates of lactic acid production rate and oxygen consumption. CONCLUSIONS: Disc cell metabolism in air and at pH 7.4 differs markedly from that found in the disc nucleus in vivo, where low levels of oxygen, glucose, and pH all coexist.

Cell viability in scoliotic discs in relation to disc deformity and nutrient levels.

STUDY DESIGN: Intervertebral disc tissue was analyzed during or removed at routine surgery for correction of scoliosis. Tissue was analyzed for glucose, lactate, oxygen, glycosaminoglycan, collagen concentrations, and cell viability. OBJECTIVES: To investigate the cell viability of the scoliotic disc on the concave and convex sides and in relation to curve apex, and to relate cell viability to concentrations of nutrients, metabolites, and extracellular matrix components. SUMMARY OF BACKGROUND DATA: Compositional differences have been measured in relation to the deformation of scoliotic discs. However, the causes of these in relation to cellular activity or viability are unknown. METHODS: Oxygen concentration was measured at surgery using a microelectrode. A segment of disc then was removed and sections at defined locations measured for cell viability and glucose, lactate, glycosaminoglycan, and collagen concentrations. RESULTS Cell viability was lower toward the convex side of the curve, with the greatest difference between the sides in the apical disc. The apical disc had the lowest oxygen and highest lactate concentrations, and lowest total number of cells. Glucose concentration correlated with the number of live cells. Concentrations of glycosaminoglycans and collagen per dry weight of tissue were similar on both sides of the disc. CONCLUSIONS: Differences in cell viability correlated with changes in nutrient and metabolite levels, and also with disc deformity (convex concave and distance from curve apex). Thus asymmetrical loads, tissue deformation, and nutrient supply may work separately or in combination to cause cell death. A loss of matrix macromolecules was not seen, possibly because the period between cell death and surgery was too short, as compared with long matrix turnover times. Cell death is expected eventually to have a deleterious effect on cell matrix and disc function.