The chronic fatigue syndrome and hyperventilation

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Does Manual Therapy Provide Additional Benefit To Breathing Retraining In The Management Of Dysfunctional Breathing? A Randomised Controlled Trial

Purpose: Dysfunctional breathing (DB) is associated with an abnormal breathing pattern, unexplained breathlessness and significant patient morbidity. Treatment involves breathing retraining through respiratory physiotherapy. Recently, manual therapy (MT) has also been used, but no evidence exists to validate its use. This study sought to investigate whether MT produces additional benefit when compared with breathing retraining alone in patients with DB. Methods: Sixty subjects with primary DB were randomised into either breathing retraining (standard treatment; n¼30) or breathing retraining plus MT (intervention; n¼30) group. Both the groups received standardised respiratory physiotherapy, which included: DB education, breathing retraining, home regimen, and audio disc. Intervention group subjects additionally received MT following further assessment. Data from 57 subjects were analysed. Results: At baseline, standard treatment group subjects were statistically younger (41.7 + 13.5 versus 50.8 + 13.0 years; p¼0.001) with higher Nijmegen scores (38.6 + 9.5 versus 31.5 + 6.9; p¼0.001). However, no significant difference was found between the groups for primary outcome Nijmegen score (95% CI ( 1.1, 6.6) p¼0.162), or any secondary outcomes (Hospital Anxiety & Depression Score, spirometry or exercise tolerance). Conclusion: Breathing retraining is currently the mainstay of treatment for patients with DB. The results of this study suggest MT provides no additional benefit in this patient group.Juliana Burgess, Dr Robert Wilson, Royal Brompton & Harefield NHS Foundation Trust, and Dr Andy Jones fo

Deficient serotonin neurotransmission and depression-like serotonin biomarker alterations in tryptophan hydroxylase 2 (Tph2) loss-of-function mice

Probably the foremost hypothesis of depression is the 5-hydroxytryptamine (5-HT, serotonin) deficiency hypothesis. Accordingly, anomalies in putative 5-HT biomarkers have repeatedly been reported in depression patients. However, whether such anomalies in fact reflect deficient central 5-HT neurotransmission remains unresolved. We employed a naturalistic model of 5-HT deficiency, the tryptophan hydroxylase 2 (Tph2) R439H knockin mouse, to address this question. We report that Tph2 knockin mice have reduced basal and stimulated levels of extracellular 5-HT (5-HTExt). Interestingly, cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and fenfluramine-induced plasma prolactin levels are markedly diminished in the Tph2 knockin mice. These data seemingly confirm that low CSF 5-HIAA and fenfluramine-induced plasma prolactin reflects chronic, endogenous central nervous system (CNS) 5-HT deficiency. Moreover, 5-HT1A receptor agonist-induced hypothermia is blunted and frontal cortex 5-HT2A receptors are increased in the Tph2 knockin mice. These data likewise parallel core findings in depression, but are usually attributed to anomalies in the respective receptors rather than resulting from CNS 5-HT deficiency. Further, 5-HT2A receptor function is enhanced in the Tph2 knockin mice. In contrast, 5-HT1A receptor levels and G-protein coupling is normal in Tph2 knockin mice, indicating that the blunted hypothermic response relates directly to the low 5-HTExt. Thus, we show that not only low CSF 5-HIAA and a blunted fenfluramine-induced prolactin response, but also blunted 5-HT1A agonist-induced hypothermia and increased 5-HT2A receptor levels are bona fide biomarkers of chronic, endogenous 5-HT deficiency. Potentially, some of these biomarkers could identify patients likely to have 5-HT deficiency. This could have clinical research utility or even guide pharmacotherapy

Resting and Post Bronchial Challenge Testing Carbon Dioxide Partial Pressure in Individuals with and without Asthma

Objective: There is conflicting evidence about resting carbon dioxide levels in asthmatic individuals. We wanted to determine if transcutaneously measured carbon dioxide levels prior and during bronchial provocation testing differ according to asthma status reflecting dysfunctional breathing. Methods: We investigated active firefighters and policemen by means of a validated questionnaire on respiratory symptoms, spirometry, bronchial challenge testing with methacholine (MCT) and measurement of transcutaneous blood carbon dioxide partial pressure (PtcCO 2) at rest prior performing spirometry, one minute and five minutes after termination of MCT. A respiratory physician blinded to the PtcCO2 results assigned a diagnosis of asthma after reviewing the available study data and the files of the workers medical screening program. Results: The study sample consisted of 128 male and 10 female individuals. Fifteen individuals (11%) had physiciandiagnosed asthma. There was no clinically important difference in median PtcCO 2 at rest, one and five minutes after recovery from MCT in asthmatics compared to non-asthmatics (35.6 vs 35.7 mmHg, p = 0.466; 34.7 vs 33.4 mmHg, p = 0.245 and 37.4 vs 36.4 mmHg, p = 0.732). The median drop in PtcCO2 during MCT and the increase after MCT was lower in asthmatics compared to non-asthmatics (0.1 vs 3.2 mmHg, p = 0.014 and 1.9 vs 2.9 mmHg, p = 0.025). Conclusions: PtcCO2 levels at rest prior and during recovery after MCT do not differ in individuals with or without physicia

On the Role of the Difference in Surface Tensions Involved in the Allosteric Regulation of NHE-1 Induced by Low to Mild Osmotic Pressure, Membrane Tension and Lipid Asymmetry

The sodium-proton exchanger 1 (NHE-1) is a membrane transporter that exchanges Na+ for H+ ion across the membrane of eukaryotic cells. It is cooperatively activated by intracellular protons, and this allosteric regulation is modulated by the biophysical properties of the plasma membrane and related lipid environment. Consequently, NHE-1 is a mechanosensitive transporter that responds to osmotic pressure, and changes in membrane composition. The purpose of this study was to develop the relationship between membrane surface tension, and the allosteric balance of a mechanosensitive transporter such as NHE-1. In eukaryotes, the asymmetric composition of membrane leaflets results in a difference in surface tensions that is involved in the creation of a reservoir of intracellular vesicles and membrane buds contributing to buffer mechanical constraints. Therefore, we took this phenomenon into account in this study and developed a set of relations between the mean surface tension, membrane asymmetry, fluid phase endocytosis and the allosteric equilibrium constant of the transporter. We then used the experimental data published on the effects of osmotic pressure and membrane modification on the NHE-1 allosteric constant to fit these equations. We show here that NHE-1 mechanosensitivity is more based on its high sensitivity towards the asymmetry between the bilayer leaflets compared to mean global membrane tension. This compliance to membrane asymmetry is physiologically relevant as with their slower transport rates than ion channels, transporters cannot respond as high pressure-high conductance fast-gating emergency valves

Invloed van dagdosering en inhalatiesysteem op therapieontrouw bij astmapatiënten

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