The added value of haemoglobin to height, age, and sex to predict DLCO in subjects with preserved exercise capacity.

BACKGROUND: The single breath diffusion capacity for carbon monoxide (DLCO) captures several aspects of the role of the lung in meeting the metabolic demands of the body. The magnitude of the independent contributors to the DLCO is unknown. The aim of this study was to investigate the factors that independently contribute to the DLCO. OBJECTIVES: The objective was to investigate the impact of height, age, sex and haemoglobin on DLCO, alveolar volume (VA) and carbon monoxide transfer coefficient (KCO). METHODS: Study participants were pre-screened based on normal exercise capacity achieved during an incremental cardio-pulmonary exercise testing (CPET) using cycle ergometry at McMaster University Medical Center between 1988-2012. Participants who had an FEV1>80% predicted, with an FEV1/FVC ≥0.7 and who achieved a maximum power output ≥80% were selected for analysis. In total, 16,298 subjects [61% male, mean height 1.70m (range 1.26-2.07), age 49 yrs (10-94), weight 79 kg (23-190) had DLCO measured while demonstrating normal spirometry and exercise capacity. RESULTS: The DLCO increased exponentially with height, was 15% greater in males, increased with age yearly until 20, then decreased yearly after the age of 35, and was 6% higher per gram of haemoglobin (5.58*Height(m)1.69*1.15 in Males*(1-0.006*Age>35)*(1+0.01*Age<20) *(1+0.06*Hb gm/dl), (r = 0.76). CONCLUSION: Height, age, sex, and haemoglobin all have independent influence on the DLCO in subjects with normal spirometry and preserved exercise capacity.

Comparison of ventilation defects quantified by Technegas SPECT and hyperpolarized 129Xe MRI.

Introduction: The ideal contrast agents for ventilation SPECT and MRI are Technegas and 129Xe gas, respectively. Despite increasing interest in the clinical utility of ventilation imaging, these modalities have not been directly compared. Therefore, our objective was to compare the ventilation defect percent (VDP) assessed by Technegas SPECT and hyperpolarized 129Xe MRI in patients scheduled to undergo lung cancer resection with and without pre-existing obstructive lung disease. Methods: Forty-one adults scheduled to undergo lung cancer resection performed same-day Technegas SPECT, hyperpolarized 129Xe MRI, spirometry, and diffusing capacity of the lung for carbon monoxide (DLCO). Ventilation abnormalities were quantified as the VDP using two different methods: adaptive thresholding (VDPT) and k-means clustering (VDPK). Correlation and agreement between VDP quantified by Technegas SPECT and 129Xe MRI were determined by Spearman correlation and Bland-Altman analysis, respectively. Results: VDP measured by Technegas SPECT and 129Xe MRI were correlated (VDPT: r = 0.48, p = 0.001; VDPK: r = 0.63, p < 0.0001). A 2.0% and 1.6% bias towards higher Technegas SPECT VDP was measured using the adaptive threshold method (VDPT: 23.0% ± 14.0% vs. 21.0% ± 5.2%, p = 0.81) and k-means method (VDPK: 9.4% ± 9.4% vs. 7.8% ± 10.0%, p = 0.02), respectively. For both modalities, higher VDP was correlated with lower FEV1/FVC (SPECT VDPT: r = -0.38, p = 0.01; MRI VDPK: r = -0.46, p = 0.002) and DLCO (SPECT VDPT: r = -0.61, p < 0.0001; MRI VDPK: r = -0.68, p < 0.0001). Subgroup analysis revealed that VDP measured by both modalities was significantly higher for participants with COPD (n = 13) than those with asthma (n = 6; SPECT VDPT: p = 0.007, MRI VDPK: p = 0.006) and those with no history of obstructive lung disease (n = 21; SPECT VDPT: p = 0.0003, MRI VDPK: p = 0.0003). Discussion: The burden of ventilation defects quantified by Technegas SPECT and 129Xe MRI VDP was correlated and greater in participants with COPD when compared to those without. Our observations indicate that, despite substantial differences between the imaging modalities, quantitative assessment of ventilation defects by Technegas SPECT and 129Xe MRI is comparable.

CFTR heterozygosity in severe asthma with recurrent airway infections: a retrospective review.

RATIONALE: Patients with asthma who have neutrophilic bronchitis may have an underlying cause leading to increased susceptibility to airway infections. METHODS: Retrospective review of patients with asthma who had a previous history of recurrent exacerbations that had been associated with airway or sinus infections referred to a tertiary asthma center between 2005 and 2020. Demographics, clinical features, and airway inflammation type determined by sputum cytometry were compared between CFTR carriers and non-carriers. Multiple linear regression was used to identify clinical predictors of CFTR carrier status. Response to nebulized hypertonic saline was assessed by comparing the number of infective exacerbations before and after its initiation. RESULTS: 75 patients underwent CFTR mutation testing. Of these, 13 (17%) were CFTR carriers. The most common mutation was [Formula: see text]F508. CFTR carriers were older (adjusted odds ratio 1.06 (CI 95% 1.01, 1.13)) and had more frequent flares requiring hospitalization (4.19 (1.34, 24.74)). Neutrophilic airway inflammation was the most common inflammatory subtype in CFTR carriers, though 8/13 also had eosinophilic bronchitis. Nebulized hypertonic saline was well tolerated by most and reduced the frequency of infective exacerbations. CONCLUSIONS: The prevalence of CFTR heterozygosity in this cohort with recurrent neutrophilic bronchitis is higher than in the general population. Respiratory disease in CFTR carriers is associated with older age and may cause significant morbidity. Airway neutrophilia is the most common inflammatory subtype, but > 50% had eosinophilic bronchitis requiring treatment. Hypertonic saline appears to be well tolerated and effective in reducing the number of infective exacerbations.

Exercise-induced bronchoconstriction and bronchodilation: investigating the effects of age, sex, airflow limitation and FEV1.

Exercise-induced bronchoconstriction (EIBc) is a recognised response to exercise in asthmatic subjects and athletes but is less well understood in an unselected broad population. Exercise-induced bronchodilation (EIBd) has received even less attention. The objective of this study was to investigate the effects of age, sex, forced expiratory volume in 1 s (FEV1) and airflow limitation (FEV1/forced vital capacity (FVC) <0.7) on the prevalence of EIBc and EIBd.This was a retrospective study based on incremental cardiopulmonary exercise testing on cycle ergometry to symptom limitation performed between 1988 and 2012. FEV1 was measured before and 10 min after exercise. EIBc was defined as a percentage fall in FEV1 post-exercise below the 5th percentile, while EIBd was defined as a percentage increase in FEV1 above the 95th percentile.35 258 subjects aged 6-95 years were included in the study (mean age 53 years, 60% male) and 10.3% had airflow limitation (FEV1/FVC <0.7). The lowest 5% of subjects demonstrated a ≥7.6% fall in FEV1 post-exercise (EIBc), while the highest 5% demonstrated a >11% increase in FEV1 post-exercise (EIBd). The probability of both EIBc and EIBd increased with age and was highest in females across all ages (OR 1.76, 95% CI 1.60-1.94; p<0.0001). The probability of EIBc increased as FEV1 % pred declined (<40%: OR 4.38, 95% CI 3.04-6.31; p<0.0001), with a >2-fold increased likelihood in females (OR 2.31, 95% CI 1.71-3.11; p<0.0001), with a trend with airflow limitation (p=0.06). The probability of EIBd increased as FEV1 % pred declined, in the presence of airflow limitation (OR 1.55, 95% CI 1.24-1.95; p=0.0001), but sex had no effect.EIBc and EIBd can be demonstrated at the population level, and are influenced by age, sex, FEV1 % pred and airflow limitation.

The Impact of beta blockade on the cardio-respiratory system and symptoms during exercise.

BACKGROUND: Beta blockers prolong life in patients with cardiovascular diseases. Negative chronotropic and inotropic effects carry the potential to adversely effect peripheral skeletal and airway smooth muscle contributing to further fatigue, dyspnea and exercise intolerance. RESEARCH QUESTIONS: Do beta-blockers reduce maximal power output (MPO), VO2 max, cardiorespiratory responses, increase the perceived effort required to cycle and breath during cardiopulmonary exercise tests (CPET) and limit the capacity to exercise? METHODS: Retrospective observational study of subjects performing CPET to capacity from 1988 to 2012. Subjects with and without beta-blockers were compared: baseline physiological characteristics, MPO, VO2 max, heart rate max, ventilation responses and perceived exertion required to cycle and breathe (modified Borg scale). Forward stepwise linear additive regression was performed with MPO as the dependent factor with height, age, gender, muscle strength, FEV1 and DLCO as independent contributors. RESULTS: 42,771 subjects were included 7,787 were receiving beta-blocker [mean age 61 yrs, BMI 28.40 kg/m2, 9% airflow obstruction (FEV1/FVC<0.7)] and 34,984 were not [mean age 51yrs, BMI 27.40 kg/m2, 11% airflow obstruction]. Heart rate was lower by 18.2% (95% C.I. 18.15-18.38) (p<0.0001) while Oxygen pulse (VO2/HR) was higher by 19.5% (95% C.I. 19.3-19.7) in those receiving beta blockers. Maximum power output (MPO) was 3.3% lower in those taking beta-blockers. The perceived effort required to cycle and breathe (mBorg) was 8% lower in those taking beta-blockers. INTERPRETATION: Increases in oxygen pulse minimize the reduction in exercise intolerance and symptom handicap associated with beta-blockers.

Publisher Correction: Pyroglutamic acidosis as a cause for high anion gap metabolic acidosis: a prospective study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Pyroglutamic acidosis as a cause for high anion gap metabolic acidosis: a prospective study.

5-oxoprolinemia (pyroglutamic acid, PGA) in the absence of acetaminophen use has been rarely reported as a cause for high anion gap metabolic acidosis. We investigated the prevalence and risk factors for elevated PGA concentrations among hospitalized patients with high anion gap metabolic acidosis: We prospectively enrolled patients with high anion gap metabolic acidosis hospitalized in the department of medicine. For each patient we collected the main diagnosis, concurrent medications and laboratory parameters. Spot urine samples were tested for PGA concentration. Levels ≥63 µmol/mmol creatinine were considered elevated. Overall, forty patients were prospectively followed. Mean age was 66.9 (17.9) years. Four (6.3%) patients had a high urine PGA level and demonstrated also lower blood pH (7.2 vs 7.3, p = 0.05) and lower serum lactate concentration (17.5 mg/dl vs 23.0 mg/dl, p = 0.04). Additionally, the high PGA level group consisted of more patients with septic shock [2/4 (50%) vs 3/36 (8.3%)] with a trend towards significance (p = 0.07). In conclusion, PGA might have a role in patients with septic shock and acidosis. Being a treatable condition, PGA should be taken into consideration particularly when no other cause for high anion gap is identified.

Low rate of spleen involvement in sporadic Burkitt lymphoma at staging on PET-CT.

BACKGROUND: Burkitt lymphoma is a highly aggressive B cell non-Hodgkin lymphoma. Cross-sectional imaging techniques that are used to detect liver and spleen involvement by lymphoma have high rates of false negative and false positive findings, and as such may reduce the accuracy of staging. PURPOSE: This retrospective study evaluated the use of FDG PET-CT in determining splenic involvement at staging, in a relatively large cohort of adult patients with the sporadic form of Burkitt lymphoma (SBL). PATIENTS AND METHODS: All adult patients who underwent FDG PET-CT for staging of SBL at one medical center during 2005-2014 were enrolled for this retrospective study. RESULTS: Data were analyzed of 20 patients, with median age 49 years; 17 were male. PET-CT revealed highly intense FDG uptake, mean SUV max 11.4 ± 7.49 (range 4.3-38) in various tissues. None of the 20 patients had either focal or diffuse increased uptake of FDG in the spleen parenchyma. In 2 patients, there were highly FDG-avid soft tissue masses adjacent to the spleen, both in the context of direct peritoneal disease extension. CONCLUSION: The spleen is rarely involved in SBL at the time of staging, according to PET-CT, except in cases with direct extension from adjacent peritoneal mass. The low rate of spleen involvement according to PET-CT may serve as a specific characteristic of SBL. Larger-scale clinical studies incorporating PET-CT scans in SBL are needed to confirm our observation.

Hypermagnesuria in Humans Following Acute Intravenous Administration of Digoxin.

BACKGROUND: Hypomagnesemia is a known predisposing condition for the appearance of digitalis toxicity. The detection of a genetic form of Mg urinary wasting with hypomagnesemia being caused by a mutation in the γ subunit (FXYD2) of the Na,K-ATPase, the pharmacological target of Digoxin, prompted us to investigate whether Digoxin administration increases urinary Mg excretion. METHODS: Two groups of subjects, with rapid atrial fibrillation, received intravenous Digoxin (n = 9) or verapamil (n = 8), for heart rate control. During the following 4 h, blood and urinary creatinine, sodium, potassium, calcium, and magnesium levels were determined, and fractional excretion (Fex) values for Na, K, Ca, and Mg were calculated. RESULTS: In the Digoxin group, at 60 min Fex Mg rose from 3.07 ± 1.21 to 7.58 ± 2.51% (an increase of 269 ± 107% of baseline, p < 0.001), and at 240 min to 6.05 ± 2.30% (204 ± 56% of baseline, p < 0.01). No significant change was observed for Fex Na, Fex K, and Fex Ca. A striking correlation was found between individual values of Fex Mg and serum Digoxin concentration (r = 0.678, p < 0.0001). No significant correlation was found between Fex Na or Fex K and serum Digoxin. A correlation of borderline significance was found between Fex Ca and serum Digoxin (r = 0.349, p = 0.073). CONCLUSIONS: The hypermagnesuric effect of acute Digoxin treatment is reminiscent of the effect of the missense mutation in FXYD2, which assumes that FXYD2 is a positive regulator of Na,K-ATPase in the distal convoluted tubule (DCT). The borderline calciuric effect of Digoxin may point to an additional site of action, more proximal to the DCT, that is, the thick ascending limb.

Human cytomegalovirus viral load in tumor and peripheral blood samples of patients with malignant gliomas.

Malignant gliomas are the most common primary brain tumors in adults. The disease has no known etiology, progresses rapidly, and is fatal despite current therapies. Human cytomegalovirus (HCMV) is a beta herpes virus that is trophic for glial cells and infects 50% to 90% of the adult human population. HCMV-mediated disease in immunosuppressed patients has highlighted the possible role of this virus in the development of other diseases, particularly inflammatory diseases such as vascular diseases, autoimmune diseases, and certain malignancies. Sensitive detection of viral DNA, mRNA, and antigens in tumor tissues, as well as seroepidemiologic evidence, suggest a link between HCMV and several human malignancies. HCMV gene products are proposed to dysregulate multiple cellular pathways involved in oncogenesis, such as cell cycle regulation, apoptosis, migration, and angiogenesis. These theories, currently being researched, suggest that HCMV acts as an oncomodulator in malignancies. We investigated the association between HCMV infection and reactivation, and malignant gliomas. An open, matched case-control, parallel group pilot study was performed in a tertiary referral center. The HCMV viral load in peripheral blood and tumor samples of 19 patients newly diagnosed with glioblastoma multiforme was compared with a matched control cohort comprising 19 patients newly diagnosed with non-malignant brain tumors. There was no significant correlation between peripheral blood and tumor tissue HCMV viral load in patients with glioblastoma multiforme compared to the control cohort. The findings of the present study did not support an oncomodulatory role for HCMV in malignant gliomas.