Effectiveness of steam inhalation and nasal irrigation for chronic or recurrent sinus symptoms in primary care: a pragmatic randomized controlled trial.

BACKGROUND: Systematic reviews support nasal saline irrigation for chronic or recurrent sinus symptoms, but trials have been small and few in primary care settings. Steam inhalation has also been proposed, but supporting evidence is lacking. We investigated whether brief pragmatic interventions to encourage use of nasal irrigation or steam inhalation would be effective in relieving sinus symptoms. METHODS: We conducted a pragmatic randomized controlled trial involving adults (age 18-65 yr) from 72 primary care practices in the United Kingdom who had a history of chronic or recurrent sinusitis and reported a "moderate to severe" impact of sinus symptoms on their quality of life. Participants were recruited between Feb. 11, 2009, and June 30, 2014, and randomly assigned to 1 of 4 advice strategies: usual care, daily nasal saline irrigation supported by a demonstration video, daily steam inhalation, or combined treatment with both interventions. The primary outcome measure was the Rhinosinusitis Disability Index (RSDI). Patients were followed up at 3 and 6 months. We imputed missing data using multiple imputation methods. RESULTS: Of the 961 patients who consented, 871 returned baseline questionnaires (210 usual care, 219 nasal irrigation, 232 steam inhalation and 210 combined treatment). A total of 671 (77.0%) of the 871 participants reported RSDI scores at 3 months. Patients' RSDI scores improved more with nasal irrigation than without nasal irrigation by 3 months (crude change -7.42 v. -5.23; estimated adjusted mean difference between groups -2.51, 95% confidence interval -4.65 to -0.37). By 6 months, significantly more patients maintained a 10-point clinically important improvement in the RSDI score with nasal irrigation (44.1% v. 36.6%); fewer used over-the-counter medications (59.4% v. 68.0%) or intended to consult a doctor in future episodes. Steam inhalation reduced headache but had no significant effect on other outcomes. The proportion of participants who had adverse effects was the same in both intervention groups. INTERPRETATION: Advice to use steam inhalation for chronic or recurrent sinus symptoms in primary care was not effective. A similar strategy to use nasal irrigation was less effective than prior evidence suggested, but it provided some symptomatic benefit. TRIAL REGISTRATION: ISRCTN, no. 88204146.

Effects of acupuncture as a treatment for hyperventilation syndrome: a pilot, randomized crossover trial.

BACKGROUND: Sustained and subtle hyperventilation can result in a wide variety of symptoms, leading to a chronic condition that has been termed hyperventilation syndrome (HVS). Treatment options include physiotherapy, in the form of breathing retraining (BR), but additional approaches aim to reduce the anxiety that is recognized as being a frequent component of this condition. OBJECTIVES: The aim of this study was to evaluate whether acupuncture is an appropriate treatment for HVS to reduce anxiety, and whether a crossover trial is an appropriate study design to evaluate acupuncture in this condition. DESIGN: A single-blind crossover trial was carried out comparing the effects of 4 weeks (30 minutes twice weekly) acupuncture and BR on patients with HVS. SUBJECTS: Ten (10) patients diagnosed with HVS were recruited to the trial and randomized into two groups. Both groups received acupuncture and BR with a washout period of 1 week. OUTCOME MEASURES: The primary outcome measure used was the Hospital Anxiety and Depression (HAD) Scale. Other outcome measures used were the Nijmegen questionnaire and Medical Research Council Dyspnea scale. RESULTS: The results showed statistically significant treatment differences between acupuncture and breathing retraining, in favor of acupuncture. Reductions were found in the HAD A (anxiety) (p = 0.02) and Nijmegen (symptoms) (p = 0.03) scores. There was no statistical evidence of any carryover effects. However, when graphically examining individual anxiety scores, in those who received acupuncture first, there was a reduction in anxiety levels which persisted through the washout period, suggesting that there may have been some carryover effect from this treatment. CONCLUSIONS: This study suggests that acupuncture may be beneficial in the management of HVS in terms of reducing anxiety levels and symptom severity. However, there may be some carryover effect, after acupuncture treatment, which went undetected because the small sample size. This preliminary study provides the basis for a larger, sufficiently powered and methodologically sound trial.

High-dose fish oil and antioxidants in Crohn's disease and the response of bone turnover: a randomised controlled trial.

Crohn's disease is associated with altered bone turnover that may be influenced by nutritional status, the systemic inflammatory response, cytokine production by circulating (peripheral blood) mononuclear cells (PBMC) and antioxidant micronutrient intake. High-dose fish oil is associated with reductions in disease relapse and inflammatory markers, and modulates PBMC function. The effect of fish oil plus antioxidants on bone turnover and PBMC function (the production of interferon-gamma and prostaglandin E2) in Crohn's disease was investigated in a randomised-controlled trial. Patients with currently or recently raised biochemical markers of inflammation (C-reactive protein > or = 6.9 mg/l or erythrocyte sedimentation rate > or =18 mm/h) received fish oil (providing 2.7 g/d EPA and DHA) and antioxidants (vitamins A, C and E, and Se) (n 31) or placebo (n 30) for 24 weeks. Bone turnover was assessed by measuring the concentrations of urinary deoxypyridinoline (bone resorption) and serum osteocalcin (bone formation). Fish oil plus antioxidants were associated with increases in EPA, DHA Se in plasma (all P < 0.01), and with a reduction in interferon-gamma production by mitogen-stimulated PBMC, which demonstrated a negative correlation with deoxypyridinoline/creatinine:osteocalcin ratio (r - 0.33, P = 0.009). There were no differences between the groups at 24 weeks in the response of deoxypyridinoline or osteocalcin or their ratio, or in nutritional status. Dietary supplementation in Crohn's disease with high intakes of EPA and DHA, as fish oil, plus antioxidants was associated with a modulated production of interferon-gamma by PBMC but not altered indices of bone turnover.

Fish oil and antioxidants alter the composition and function of circulating mononuclear cells in Crohn disease.

BACKGROUND: Crohn disease (CD) is associated with osteoporosis and other extraintestinal manifestations that might be mediated by cytokines from circulating (peripheral blood) mononuclear cells (PBMCs). Fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduces disease activity in patients with CD with raised laboratory markers of inflammation and in healthy subjects alters PBMC function. OBJECTIVE: We investigated the effect of fish oil plus antioxidants on cytokine production by PBMCs from patients with CD with raised C-reactive protein concentrations (>/=6.9 mg/L) or erythrocyte sedimentation rates (>/=18 mm/h). DESIGN: A randomized placebo-controlled trial of fish oil (2.7 g EPA and DHA/d; n = 31) or placebo (olive oil; n = 31) for 24 wk was conducted in patients with CD. The fish-oil group additionally received an antioxidant preparation (vitamins A, C, and E and selenium). Exclusion criteria included corticosteroid use. Fatty acid composition was measured by gas chromatography. Production of tumor necrosis factor alpha, interferon gamma (IFN-gamma), and prostaglandin E(2) (PGE(2)) was measured by enzyme-linked immunosorbent assays after stimulation with mitogen and endotoxin (lipopolysaccharide). RESULTS: Fish-oil plus antioxidant dietary supplementation was associated with higher EPA and DHA incorporation into PBMCs (P < 0.001) and lower arachidonic acid (P = 0.006) and lower production of IFN-gamma by mitogen-stimulated PBMCs (P = 0.012) and of PGE(2) by lipopolysaccharide-stimulated PBMCs (P = 0.047). CONCLUSION: Dietary supplementation with fish oil plus antioxidants is associated with modified PBMC composition and lower production of PGE(2) and IFN-gamma by circulating monocytes or macrophages. The response of extraintestinal manifestations of CD should be investigated in a randomized controlled trial.

Peripheral blood mononuclear cell fatty acid composition and inflammatory mediator production in adult Crohn's disease.

BACKGROUND & AIMS: Crohn's disease (CD) is associated with nutritional deficiencies, altered plasma concentrations of polyunsaturated fatty acids (PUFA) and an anti-inflammatory response to fish oil that contains n-3 PUFA. This suggests that, in CD, immune cells may have altered n-3 PUFA composition with functional consequences. The aim of this study is to investigate n-3 and n-6 PUFA composition and synthetic function of peripheral blood mononuclear cells (PBMC) in the basal state. METHODS: A case control study of 52 adult CD patients and healthy, age- and sex-matched controls. Composition of PBMC and plasma phospholipids were measured by gas chromatography and production of tumour necrosis factor-alpha, prostaglandin E2 (PGE2) and interferon-gamma (IFN-gamma) by PBMC were measured by ELISA. RESULTS: CD was associated with higher concentrations of eicosapentaenoic acid and other n-3 PUFA, and lower arachidonic acid (AA) (n-6 PUFA) in PBMC. This was not explained by differences in dietary fat intake. Lower rates of production of PGE2 and IFN-gamma by PBMC were noted in quiescent and active CD, respectively, compared to controls. CONCLUSIONS: CD is associated with a greater availability, and not a deficiency, of n-3 PUFA in PBMC, but lower concentrations of AA, and lower rates of production of PGE2 and IFN-gamma, compared to healthy controls.

Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant cosupplementation.

BACKGROUND: Prostaglandin E(2) (PGE(2)) inhibits lymphocyte proliferation and the production of interferon-gamma (IFN-gamma) by peripheral blood mononuclear cells, but the effect of PGE(2) on interleukin 4 (IL-4) production is unclear. Fish oil, which contains eicosapentaenoic and docosahexaenoic acids, inhibits production of PGE(2). The effects of fish oil on lymphocyte proliferation and production of IFN-gamma and IL-4 are unclear and may be influenced by the availability of antioxidants. OBJECTIVE: We investigated the effect of dietary fish oil with and without antioxidant cosupplementation on lymphocyte proliferation and the production of PGE(2), IFN-gamma, and IL-4 by peripheral blood mononuclear cells. DESIGN: Sixteen healthy men received dietary fish-oil supplements providing 0.3, 1, and 2 g eicosapentaenoic acid plus docosahexaenoic acid/d for 4 consecutive weeks each (total of 12 wk). All subjects were randomly assigned to daily cosupplementation with either antioxidants (200 microg Se, 3 mg Mn, 30 mg RRR-alpha-tocopheryl succinate, 90 mg ascorbic acid, 450 micro g vitamin A) or placebo. RESULTS: Fish-oil supplementation decreased PGE(2) production and increased IFN-gamma production and lymphocyte proliferation from baseline values. Cosupplementation with antioxidants did not affect cytokine production or lymphocyte proliferation. CONCLUSION: Dietary fish oil modulates production of IFN-gamma and lymphocyte proliferation in a manner consistent with decreased production of PGE(2), but this effect is not modified by antioxidant cosupplementation.