Sleep Quality and the Common Cold: Where Are the Data?
Sleep Quality and the Common Cold: Where Are the Data?
Abstract & Commentary
By Joseph Varon, MD, FACP, FCCP, FCCM, Clinical Professor of Internal Medicine, University of Texas Health Science Center, Houston; Adjunct Professor of Medicine, University of Texas Medical Branch, Galveston. Dr. Varon reports no financial relationship to this field of study.
Synopsis: Lack of sleep impairs the immune system and lowers resistance to viral illness. The quality of sleep is important. Those volunteers who spent less than 92% of their time in bed asleep were five-and-a-half times more likely to become ill than those who were asleep for at least 98% of their time in bed.
Source: Cohen S, et al. Sleep habits and susceptibility to the common cold. Arch Intern Med 2009;169:62-67.
This study was aimed at evaluating whether sleep habits are associated with resistance to the common cold. The investigators obtained estimates of sleep habits of volunteers that reported sleep duration, sleep efficiency, and "feeling rested" the next day for a period of 14 consecutive days. In addition, virus-specific neutralizing antibody titers, demographics, and height and weight were obtained in these previously healthy volunteers. Once the baseline sleep assessments were completed and the antibody titers were obtained, volunteer participants were exposed to a rhinovirus (RV-39) and were closely monitored on a daily basis to see whether they developed the clinical syndrome of the "common cold." All signs and symptoms of illness were assessed the day before and for a period of 5 days after the viral challenge.
The study data were collected over a 4-year period and the study included 78 healthy men and 75 women (age range, 21-55 years). All participants were interviewed by phone on 14 consecutive evenings utilizing questions from the Pittsburgh Sleep Quality Index. To avoid bias, viral immunity was assessed by the pre-challenge antibody titer and age considerations, as well as by body mass index, gender, race, income, level of education, season of exposure, and pre-existing psychological variables. Of the 153 subjects enrolled, 135 (88.2%) were infected by the RN-39; 54 (35.3%) developed a common cold (defined as infection and the objective common cold criteria) and 66 (43.1%) developed a common cold (defined as infection and the subjective [Jackson] criteria). In this cohort, a shorter sleep duration and lower sleep efficiency were associated with increased risk for the development of a common cold by both objective and subjective criteria. The percentage of nights that the participants responded as "feeling rested" had no correlation with the presence of infection. Interestingly, sleep efficiency, but not sleep duration was associated with the total symptom score of these volunteers.
Commentary
This study showed a direct association between poorer sleep efficiency and shorter sleep duration prior to RV-39 exposure with an increased probability of developing a common cold. A number of theories exist as to why good sleep efficiency and duration could be protective for viral illness. There is a direct correlation of sleep with the regulation of a variety of pro-inflammatory cytokines, histamines, and other symptom mediators that are commonly released in response to a viral infection.1 It is well documented that people who sleep 7-8 hours a night have the lowest rates of heart disease.2 On the basis of the present study, the authors suggest a minimum of 7 hours of sleep on a daily basis.
The reader must be cautious, however, at looking at the data presented. All the volunteers were healthy prior to enrollment in this trial. In reality, in a busy clinical practice, many of our patients have other significant comorbidities that may adversely affect their chances of developing a common cold besides good sleep efficiency.
References
1. Irwin MR, et al. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med 2006;166:1756-1762.
2. Gangwisch JE, et al. Short sleep duration as a risk factor for hypertension: Analyses of the first National Health and Nutrition Examination Survey. Hypertension 2006;47:833-839.
Pharmacology Update
Fenofibric Acid Delayed-release Capsules (TriLipix™)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
The FDA has approved the first fibrate to be used in combination with a statin. Fenofibric acid is the active metabolite of fenofibrate. Abbott Laboratories will market the drug as TriLipixä.
Indications
Fenofibric acid is indicated for use in combination with a statin to reduce triglycerides (TG) and increase HDL-C in patients with mixed dyslipidemia and CHD or a CHD risk equivalent who are on optimal statin therapy to achieve their LDL-C goal.1 It is also indicated as monotherapy to reduce TG in patients with severe hypertriglyceridemia and monotherapy to reduce elevated LDL-C, total-C, TG, and Apo B, and raise HDL-C in patients with primary hyperlipidemia or mixed dyslipidemia.
Dosage
For primary hyperlipidemia or mixed dyslipidemia the dose is 135 mg once daily.1 For severe hypertriglyceridemia the dose is 45-135 mg once daily. It may be taken without regard to meals. Fenofibric acid may be taken at the same time as the statin at low-to-moderate doses. Coadministration with maximum doses of a statin has not been studied.
Fenofibric acid is available as delayed-release capsules: 45 mg and 135 mg.
Potential Advantages
Fenofibric acid, in contrast to its ester prodrug (fenofibrate), which is poorly soluble with low bioavailability, does not require enzymatic cleavage to form the active component and is well absorbed. Absorption was improved by using micronization, microcoating, or nanocrystal technology.2 Micronized fenofibrate should be taken with food to optimize absorption, while the microcoated and nanocrystal formulations can be taken without regard to meals.
Potential Disadvantages
The addition of fenofibric acid to a moderate dose of a statin showed less reduction in LDL-C than statin alone.1,3,4 Myopathy and rhabdomyolysis have been reported with fenofibrate.1 This risk may be increased when fenofibrate is combined with a statin, particularly in elderly patients and patients with diabetes, renal failure, or hypothyroidism. Fenofibric acid can elevate serum creatinine and serum transaminases; these should be monitored periodically. The effect of anticoagulants may be potentiated by fenofibric acid; therefore, monitoring of INR is recommended and dose of anticoagulant should be adjusted as appropriate. Fenofibric acid may increase the risk of cholelithiasis by increasing cholesterol excretion in the bile. Common adverse events include headache, back pain, nasopharyngitis, nausea, myalgia, diarrhea, and upper respiratory tract infection.
Comments
Fenofibric acid is the active metabolite of fenofibrate. The addition of fenofibric acid to a low-dose and moderate-dose statin was studied in three 12-week, double-blind, controlled phase III studies in patients with mixed dyslipidemia (n = 2698).1,3 Subjects had TG ≥ 150 mg/dL, HDL-C < 40 mg/dL (males) or < 50 mg/dL (females), and LDL-C ≥ 130 mg/dL. Each study randomized subjects to a low-dose or moderate-dose statin as monotherapy, combination of fenofibric acid and a statin, or fenofibric acid monotherapy. Statins used were rosuvastatin (10 mg and 20 mg), simvastatin (20 mg and 40 mg), and atorvastatin (20 mg and 40 mg). Primary endpoints were changes from baseline for LDL-C, HDL-C, and TG. Results from the pooled analysis showed that the combination increased HDL-C by 10.7% compared to low-dose statin alone and 8.8% over moderate-dose statin. TG decreased by 27.2% and 18.3%, respectively. LDL-C did not change significantly with the combination compared to low-dose statin alone. However, moderate-dose statin monotherapy showed a greater reduction than the combination (40.6% vs 34.6%). The addition of fenofibric acid to a low and moderate dose of a statin also resulted in an additional reduction in VLDL-C of 18.0% and 12.3%, respectively.1 For monotherapy in hypertriglyceridemia, primary hypercholesterolemia, and mixed dyslipidemia, the effect is expected to be similar to an equivalent dose of fenofibrate.1 Plasma levels of fenofibric acid 135 mg are similar to that produced by 145 mg (nanocrystals), 160 mg (microcoated), and 200 mg (micronized) of fenofibrate. The daily wholesale costs are $3.44 for fenofibric acid and $3.38, $1.50, and $1.94, respectively, for the different fenofibrate formulations.
Clinical Implications
Fenofibric acid is the first fibrate approved for use in combination with a statin, although this combination is commonly used in clinical practice.5,6 The combination was a component of the recently discontinued ACCORD trial which had a 2 ´ 2 design with 5800 subjects randomized to fenofibrate or placebo, with and without intensive glycemic control. Micronized and microcoated fenofibrate are available as a generic product. It is not clear if fenofibric acid provides any clinical advantage over less expensive generic fenofibrate products.
References
1. Trilipix Prescribing Information. Abbott Park, IL: Abbott Laboratories; December 2008.
2. Filippatos T, Milionis HJ. Treatment of hyperlipidaemia with fenofibrate and related fibrates. Expert Opin Investig Drugs 2008;17:1599-1614.
3. Jones PH, et al. Efficacy and safety of ABT-335 (fenofibric acid) in combination with rosuvastatin in patients with mixed dyslipidemia: A phase 3 study. Atherosclerosis 2008; doi:10:1016/j.atherosclerosis.22008.09.027.
4. Jones PH, et al. Evaluation of a new formulation of fenofibric acid, ABT-335, co-administered with statins: Study design and rationale of a phase III clinical programme. Clin Drug Investig 2008;28:625-634.
5. Cannon CP. Combination therapy in the management of mixed dyslipidaemia. J Intern Med 2008;263:353-365.
6. ATPIII Guidelines At-a-Glance Quick Desk Reference. Available at: www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf. Accessed Dec. 31, 2008.
Lack of sleep impairs the immune system and lowers resistance to viral illness. The quality of sleep is important. Those volunteers who spent less than 92% of their time in bed asleep were five-and-a-half times more likely to become ill than those who were asleep for at least 98% of their time in bed.Subscribe Now for Access
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