Habitual Fish Oil Supplementation and Incident Chronic Obstructive Pulmonary Disease: Data from a Prospective Cohort Study

Li ZH, Song WQ, Shen D, Zhang PD, et al. Clin Nutr. 2022 Oct 8;41(12):2651-2658. [CrossRef] [PubMed]

Background: Fish oil is one of the most popular supplements in the UK and other developed countries. However, the relationship between fish oil use and chronic obstructive pulmonary disease (COPD) is unclear.

Objective: To prospectively examine the association of habitual fish oil supplementation with incident COPD risk and to evaluate potential effect modification by genetic predisposition.

Methods: This study included 484,414 participants (mean and standard deviation [SD] age: 56.5 [8.1] years) from the UK Biobank who completed a touchscreen questionnaire on habitual fish oil supplement use between 2006 and 2010 and were followed up through 2018. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for sociodemographic and lifestyle behaviours, health conditions, and other potential confounding factors. A weighted genetic risk score (GRS) for COPD was derived from 112 validated single nucleotide polymorphisms.

Results: During a median follow-up of 9.0 years, 8860 incident COPD events were recorded. A total of 31.4% (152,230) of the study participants reported habitual fish oil supplementation at baseline. Habitual fish oil supplementation was significantly associated with a lower risk of incident COPD (adjusted HR: 0.88; 95% CI: 0.84-0.93). The association with COPD did not differ by GRS strata (P for interaction = 0.880). The results from subgroup and sensitivity analyses supported the robustness of our findings.

Conclusions: Our findings suggest that habitual fish oil supplementation is associated with a lower risk of incident COPD, irrespective of genetic predisposition.

Novel Bronchoscopic Interventions Appear Promising for Patients with COPD

Bowser AD. Chest Physician, November 3, 2022. Available at: https://www.mdedge.com/chestphysician/article/248210/copd/novel-bronchoscopic-interventions-appear-promising-patients-copd?channel=39313

Dr. Christian Ghattas reported on several emerging bronchoscopic treatments for patients with chronic obstructive pulmonary disease at the annual meeting of the American College of Chest Physicians (1).

Targeted Lung Denervation

Targeted lung denervation is one promising novel therapeutic option that is safe and may improve clinical outcomes. The targeted lung denervation system under study (dNerva®, Nuvaira Inc.) which involves the use of a radiofrequency catheter to ablate the peribronchial branches of the vagus nerve. The goal of disrupting pulmonary nerve input is to achieve sustained bronchodilation and reduce mucous secretion, thereby simulating the effect of anticholinergic drugs. AIRFLOW-1 demonstrated the safety and procedural success of bronchoscopic lung denervation (2). In AIRFLOW-2, a randomized, sham-controlled trial enrolling patients with symptomatic COPD targeted lung denervation plus optimal drug treatment led to fewer respiratory adverse events of interest, including hospitalizations for COPD exacerbation(3). Respiratory adverse events occurred in 32% of treated patients versus 71% of sham-treated patients in a predefined 3- to 6.5-month postprocedure window. Currently underway is AIRFLOW-3, a randomized study of targeted lung denervation versus sham procedure in patients with COPD. The study has a primary outcome measure of moderate or severe COPD exacerbations over 12 months and is slated to enroll 480 patients.

Metered Cryospray

One novel intervention with the potential to benefit patients with chronic bronchitis is metered cryospray (RejuvenAir), which works by delivering liquid nitrogen to the tracheobronchial airways. This targeted delivery ablates abnormal epithelium, facilitating the regeneration of healthy mucosa. In the study, 34 of 35 participants received three treatments 4-6 weeks apart. Investigators reported that at 3 months there were significant reductions in the COPD Assessment Test that were durable to 6 months, and changes in the St. George's Respiratory Questionnaire and the Leicester Cough Questionnaire that were durable to 9 months (4).

An ongoing randomized study called SPRAY-CB is comparing metered cryospray to sham procedure in an anticipated 210 patients with COPD with chronic bronchitis.

Bronchial Rheoplasty

Bronchial rheoplasty (RheOx, Gala Therapeutics), is another promising intervention under investigation for the treatment of chronic bronchitis.

This system delivers nonthermal pulsed electrical energy with the intention of ablating goblet cells in the airways. In 12-month results of multicenter clinical trial, bronchial rheoplasty was technically feasible and safe, with reductions in goblet cell hyperplasia and changes in patient-reported quality of life seen following the procedure (5).

A larger randomized, double-blind prospective trial with a sham control arm is underway and will include 270 patients.

References

1. Novel bronchoscopic interventions appear promising for patients with COPD Bowser AD. Chest Physician, November 3, 2022. Available at: https://www.mdedge.com/chestphysician/article/248210/copd/novel-bronchoscopic-interventions-appear-promising-patients-copd?channel=39313
2. Pison C, Shah PL, Slebos DJ, et al. Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes. Respir Res. 2021 Feb 19;22(1):62. [CrossRef] [PubMed]
3. Slebos DJ, Shah PL, Herth FJF, et al. Safety and Adverse Events after Targeted Lung Denervation for Symptomatic Moderate to Severe Chronic Obstructive Pulmonary Disease (AIRFLOW). A Multicenter Randomized Controlled Clinical Trial. Am J Respir Crit Care Med. 2019 Dec 15;200(12):1477-1486. [CrossRef] [PubMed]
4. Garner JL, Shaipanich T, Hartman JE, et al. A prospective safety and feasibility study of metered cryospray for patients with chronic bronchitis in COPD. Eur Respir J. 2020 Dec 17;56(6):2000556. [CrossRef] [PubMed]
5. Valipour A, Fernandez-Bussy S, Ing AJ, et al. Bronchial Rheoplasty for Treatment of Chronic Bronchitis. Twelve-Month Results from a Multicenter Clinical Trial. Am J Respir Crit Care Med. 2020 Sep 1;202(5):681-689. [CrossRef] [PubMed]

Sleep Apnea and Incident Unprovoked Venous Thromboembolism: Data from the French Pays de la Loire Sleep Cohort

Trzepizur W, Gervès-Pinquié C, Heude B, et al. ERS 2022 Congress. Presented Sept. 5, 2022. Abstract available at: https://k4.ersnet.org/prod/v2/Front/Program/Session?e=377&session=14833

Medscape is reporting that you can add unprovoked venous thromboembolic events to the list of potential consequences of severe obstructive sleep apnea (1). That conclusion comes from a study showing that patients with obstructive sleep apnea (OSA) who had the longest nocturnal hypoxemia episodes had a twofold risk for venous thromboembolic events. The association between nocturnal hypoxemia and VTE was strongest among patients who did not use continuous positive airway pressure (CPAP) systems, reported Wojciech Trzepizur, MD, from Angers University Hospital in Angers, France. "We found that those who spent more than 6% of their nighttime with levels of oxygen in their blood below 90% of normal had an almost twofold risk of developing VTEs as compared to patients without oxygen deprivation," he said. Trzepizur and colleagues conducted a retrospective study linking cohort data to an administrative health database. They identified unprovoked VTE in patients with a suspicion for OSA and no previous VTE. They created Cox proportional hazard models to assess the association of unprovoked VTE with apnea hypopnea index (AHI) measures and nocturnal hypoxemia markers, including the time patients spent below 90% oxygen saturation (T90), oxygen desaturation index (ODI), and hypoxic burden, defined as the total area under the respiratory event-related desaturation curve. They found that after a median follow-up of 6.3 years, 104 out of 7355 patients had an unprovoked VTE. In an unadjusted hazard model, there were significant associations between VTE and T90, as well as with hypoxic burden, but not with either AHI or ODI. However, in an analysis adjusted for age, gender, body mass index, alcohol intake,  hypertension, depression, history of cardiovascular disease, statin use, type of sleep study, study site and CPAP adherence, the investigators found that only T90 remained a significant independent predictor of VTE, with a hazard ratio (HR) of 1.06, P = .02. The association between T90 and VTE strengthened as the time spent below 90% saturation increased. Patients in the highest tercile, who spent more than 6% of the time undersaturated, had an HR for VTE of 1.95 (P = .02) compared with patients with a T90 less than 1%. There were no significant differences in VTE risk between patients who used CPAP for more than 4 hours per night compared with those who either used the devices for less than 4 hours or refused CPAP.

Reference

1. Osterweil N. Obstructive Sleep Apnea Linked to Unprovoked VTE. Medscape. September 8, 2022. Available at: https://www.medscape.com/viewarticle/980453 (accessed 9/13/2022).

Dopamine Use and Its Consequences in the Intensive Care Unit: A Cohort Study Utilizing the Japanese Intensive Care Patient Database

Suzuki R, Uchino S, Sasabuchi Y, Kawarai Lefor A, Sanui M.. Crit Care. 2022 Apr 2;26(1):90. [CrossRef] [PubMed]

Background: Dopamine is used to treat patients with shock in intensive care units (ICU) throughout the world, despite recent evidence against its use. The aim of this study was to explore the consequences of dopamine use in Japan.

Methods: The authors retrospectively searched the Japanese Intensive Care PAtient Database (JIPAD). Inclusion criteria included patients: 1) age 18 years or older, 2) admission to the ICU for reasons other than procedures, 3) ICU length of stay of 24 h or more, and 4) treatment with either dopamine or noradrenaline within 24 h of admission. The primary outcome was in-hospital mortality. Multivariable regression analysis was performed, followed by a propensity score-matched analysis.

Results: Dopamine was administered to 4,653 patients and noradrenaline to 11,844. There was no statistically significant difference in facility characteristics between frequent dopamine users (N = 28) and infrequent users (N = 28). Patients receiving dopamine had more cardiovascular diagnosis codes (70% vs. 42%; p < 0.01), more post-elective surgery status (60% vs. 31%), and lower APACHE III scores compared to patients given noradrenaline alone (70.7 vs. 83.0; p < 0.01). Multivariable analysis
showed an odds ratio for in-hospital mortality of 0.86 [95% CI: 0.71–1.04] in the dopamine ≤ 5 μg/kg/min group, 1.46 [95% CI: 1.18–1.82] in the 5–15 μg/kg/min group, and 3.30 [95% CI: 1.19–9.19] in the > 15 μg/kg/min group. In a 1:1 propensity score matching for dopamine use as a vasopressor (570 pairs), both in-hospital mortality and ICU mortality were significantly higher in the dopamine group compared to no dopamine group (22.5% vs. 17.4%, p = 0.038; 13.3%
vs. 8.8%, p = 0.018), as well as ICU length of stay (mean 9.3 days vs. 7.4 days, p = 0.004).

Conclusion: Dopamine is still widely used in Japan. The results of this study suggest detrimental effects of dopamine use specifically at a high dose. 

Reduction Of Dietary Sodium to Less Than 100 Mmol in Heart Failure (SODIUM-HF): An International, Open-Label, Randomised, Controlled Trial

Ezekowitz JA, Colin-Ramirez E, Ross H, et al. Lancet. 2022 Apr 1:S0140-6736(22)00369-5. [CrossRef] [PubMed]

Dietary restriction of sodium has been a standard of care to prevent fluid overload and adverse outcomes for patients with heart failure. To test this hypothesis, the authors conducted the SODIUM-HF study which is an international, open-label, randomized, controlled trial that enrolled patients with chronic heart failure (New York Heart Association [NYHA] functional class 2-3), and receiving optimally tolerated guideline-directed medical treatment. Patients were randomly assigned to either usual care according to local guidelines or a low sodium diet of less than 100 mmol (ie, <1500 mg/day). The primary outcome was the composite of cardiovascular-related admission to hospital, cardiovascular-related emergency department visit, or all-cause death within 12 months in the intention-to-treat (ITT) population (ie, all randomly assigned patients). 806 patients were enrolled and randomly assigned to a low sodium diet (n=397) or usual care (n=409). There was no statistical difference in mortality, hospitalizations, or emergency room visits (p>0.05 all comparisons). In ambulatory patients with heart failure, a dietary intervention to reduce sodium intake did not reduce clinical events.