Lim, Kaiser G.

Abstract Introduction Several studies have shown a positive association between Obstructive Sleep Apnea (OSA) and malignancies such as lung cancer. However, the effects of intermittent hypoxemia in cancer-free survival following curative therapy are not known. We propose that OSA-related episodic hypoxemia and hypoxic burden are independent risk factors for accelerated lung cancer reoccurrence (< 2 years). Methods We performed a retrospective record review of patients 18 years and older from January 2016 to September 2023 with history of non-small cell lung cancer who received an overnight oximetry study (OXY) within three years prior to undergoing curative malignancy treatment. Subjects with history of central sleep apnea, baseline oxygen saturation (SpO2) below 90%, receiving supplemental oxygen or treatment for OSA were excluded. Results 403 patients met inclusion criteria (52% female vs 48% males; median age 74 y). The most common histologic subtypes were adenocarcinoma (68%) followed by squamous cell carcinoma (22%). Most patients fell into Stage IA1 (35%) followed by IA2 (24.1%) and IB (19%) as per TNM 8th edition classification. Over this period, 68 patients (22%) had lung cancer recurrence (median 19 months). A 4% oxygen desaturation index (ODI) of >15 and time spent in desaturation events were found to be a risk factor for cancer reappearance in less than 2 years (p< 0.001). Measures of hypoxic burden such as time spent below 89% SpO2, average SpO2 value below 89%, and single nadir oxygen levels, showed a similar association (p< 0.001). This was irrespective of histologic subtype, stage at diagnosis, and all studied demographic variables. Basal SpO2 demonstrated no correlation. A multivariate proportional hazard survival model showed that ODI>15 was no longer significant, however average SpO2 below 89% and single minimum oxygen level remained strongly correlated with accelerated recurrence. Conclusion This study showed a strong, positive association between accelerated lung cancer recurrence and OSA-related episodic hypoxemia and hypoxic burden on our univariate analysis. The multivariate model demonstrated correlation with hypoxic load measures only, suggesting the need for a larger sample to elucidate the involvement of this highly treatable risk factor. To our knowledge, this is the first study revealing this potential link. Support (if any)

Abstract Background Pulmonary abnormalities are common in patients with prevalent heart failure (HF). Arterial hypoxemia is considered rare in HF, but this has not been rigorously evaluated in patients with HF and preserved EF (HFpEF). Methods Results Patients with HFpEF (n=539) and no clinically-relevant lung disease underwent invasive cardiopulmonary exercise testing with simultaneous blood and expired gas analysis. Exertional hypoxemia was defined by oxyhaeemoglobin saturation <94%. As compared to those without hypoxemia (n=403), patients with hypoxemia (n=136, 25%) were slightly older, heavier, and had higher NT-proBNP levels. They had higher cardiac filling pressures, higher pulmonary vascular pressures, greater alveolar-arterial O2 difference compared to those without hypoxemia. These differences were replicated in a sensitivity analysis where patients with any spirometric abnormalities were excluded. Regression analyses revealed that increases in pulmonary arterial and capillary pressures were related to lower PaO2. The presence of exertional hypoxemia was associated with two-fold increased risk for death over 2.8 (IQR 0.7-5.5) years of follow up, (Adjusted:HR 2.00 (95%CI: 1.01−3.96), p=0.046). Conclusion One quarter of HFpEF patients displayed arterial desaturation during exercise. Patients with hypoxemia display more severely abnormal hemodynamics and increased mortality. Further study is required to better understand the mechanisms in patients with HFpEF.Hemodynamic changes at rest/exerciseRisk of death in HFpEF with hypoxemia

Abstract Aims It is widely held that heart failure (HF) does not cause exertional hypoxaemia, based upon studies in HF with reduced ejection fraction, but this may not apply to patients with HF and preserved ejection fraction (HFpEF). Here, we characterize the prevalence, pathophysiology, and clinical implications of exertional arterial hypoxaemia in HFpEF. Methods and results Patients with HFpEF (n = 539) and no coexisting lung disease underwent invasive cardiopulmonary exercise testing with simultaneous blood and expired gas analysis. Exertional hypoxaemia (oxyhaemoglobin saturation <94%) was observed in 136 patients (25%). As compared to those without hypoxaemia (n = 403), patients with hypoxaemia were older and more obese. Patients with HFpEF and hypoxaemia had higher cardiac filling pressures, higher pulmonary vascular pressures, greater alveolar–arterial oxygen difference, increased dead space fraction, and greater physiologic shunt compared to those without hypoxaemia. These differences were replicated in a sensitivity analysis where patients with spirometric abnormalities were excluded. Regression analyses revealed that increases in pulmonary arterial and pulmonary capillary pressures were related to lower arterial oxygen tension (PaO2), especially during exercise. Body mass index (BMI) was not correlated with the arterial PaO2, and hypoxaemia was associated with increased risk for death over 2.8 (interquartile range 0.7–5.5) years of follow-up, even after adjusting for age, sex, and BMI (hazard ratio 2.00, 95% confidence interval 1.01–3.96; p = 0.046). Conclusion Between 10% and 25% of patients with HFpEF display arterial desaturation during exercise that is not ascribable to lung disease. Exertional hypoxaemia is associated with more severe haemodynamic abnormalities and increased mortality. Further study is required to better understand the mechanisms and treatment of gas exchange abnormalities in HFpEF.

BACKGROUND: Methacholine challenge testing (MCT) is a common bronchoprovocation technique used to assess airway hyper-responsiveness. We previously demonstrated that the addition of a viral filter to the nebulizer exhalation limb substantially reduced expelled particles during MCT. Our aim was to evaluate whether this modification affects the delivered dose of methacholine. METHODS: A mechanical ventilator was connected to a lung simulator with breathing frequency 15 breaths/min, tidal volume 500 mL, inspiratory-expiratory ratio 1:1, with a sinusoidal waveform. We compared methacholine dose delivery using the Hudson Micro Mist or AeroEclipse II BAN nebulizers powered by either a dry gas source or a compressor system. A filter placed in line between the nebulizer and test lung was weighed before and after 1 min of nebulized methacholine delivery. Mean inhaled mass was measured with and without a viral filter on the exhalation limb. Dose delivery was calculated by multiplying the mean inhaled mass by the respirable fraction (particles < 5 μm) and inhalation time. Unpaired t test was used to compare methacholine dose delivery with and without viral filter placement. RESULTS: The addition of a viral filter did not significantly affect methacholine dose delivery across all devices tested. Using a 50-psi dry gas source, dose delivered with or without a viral filter did not differ with the Hudson (422.3 μg vs 282.0 μg, P = .11) or the AeroEclipse nebulizer (563.0 μg vs 657.6 μg, P = .59). Using the compressor, dose delivered with and without a viral filter did not differ with the Hudson (974.0 μg vs 868.0 μg, P = .03) or the AeroEclipse nebulizer (818.0 μg vs 628.5 μg, P = .42). CONCLUSIONS: The addition of a viral filter to the nebulizer exhalation limb did not affect methacholine dose during bronchoprovocation testing. Routine use of a viral filter should be considered to improve pulmonary function technician safety and infection control measures during the ongoing COVID-19 pandemic.

BACKGROUND: Residual volume (RV) is a derived lung compartment that correlates with air trapping in the context of air flow obstruction on spirometry. The significance of an isolated elevation in RV in the absence of other pulmonary function test (PFT) abnormalities is not well defined. We sought to assess the clinical and radiologic findings associated with isolated elevation in RV. METHODS: We searched our out-patient PFT database at Mayo Clinic (Rochester, Minnesota) from 2016–2018 for adult patients with isolated elevation in RV. We defined isolated elevation in RV as RV ≥ upper limit of normal or ≥ 130% predicted with normal total lung capacity (TLC), spirometry, and diffusion capacity of the lung for carbon monoxide (D LCO ). We then matched this high-RV group by age and sex to an equal number of individuals with normal RV, TLC, spirometry, and D LCO (normal-RV group). RESULTS: We identified 169 subjects with isolated elevation in RV on PFTs, with a median age of 73 y; 55.6% were female, and median body mass index was 26.8 (vs 29.8 in the normal-RV group). The median RV was 3.08 L (134% predicted, interquartile range [IQR] 130–141) in the high-RV group and 2.26 L (99% predicted, IQR 90–109) in the normal-RV group (P < .001). Subjects with high RV were more likely to have smoked (54% vs 40%, P = .01) and almost twice as likely to have a maximum voluntary ventilation < 30 times the FEV 1 (21% vs 12%, P = .02). Clinically, asthma (21% vs 11%, P = .01) and non–tuberculous mycobacterial lung infections (12% vs 2%, P = .001) were more prevalent in the high-RV group. On chest computed tomography, bronchiectasis (31% vs 15%, P = .008), bronchial thickening or mucus plugging (46% vs 22%, P < .001), and emphysema (13% vs 5%, P = .046) were more common in the high-RV group. CONCLUSIONS: Isolated elevation in RV on PFTs is a clinically relevant abnormality associated with airway-centered diseases.