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Objectives: Suboptimal standards in tracheostomy care have been highlighted as a growing concern in view of the increasing demands for intensive care services. Our objective is to assess the impact of our model for tracheostomy care on patients with short-term tracheostomies (<4 months in situ) following their discharge from the intensive care unit. The model has three components: The St Mary's tracheostomy care bundle checklist, a dedicated tracheostomy multidisciplinary team and an educational programme., Design: A 38-month prospective cohort study., Setting: A London Teaching Hospital., Participants: A total of 102 patients with tracheostomy within the 19-month pre-intervention cohort and 95 patients in the 19-month post-intervention cohort., Main Outcome Measures: The number of clinical incidents, mean time taken for decannulation, mean total tracheostomy time and total number of days spent in the intensive care unit were assessed before and after the intervention., Results: Time to decannulation following intensive care unit discharge decreased from 21 to 11 days, as did the mean total tracheostomy time, from 34 to 25 days (both statistically significant with a P < 0.0001 Mann-Whitney U-test). The number of critical incidents, which included all patients prior to exclusion, substantially declined following the introduction of intervention from 58 to 7 in the second year after intervention., Conclusions: A multidisciplinary care model significantly expedited the decannulation process and reduced the overall time that a tracheostomy was in situ. The intervention was associated with a reduction in clinical incidents and shorter intensive care unit admissions, which can be associated with significant monetary savings., (© 2011 Blackwell Publishing Ltd.)

Treatment of patients with allergic asthma using low doses of peptides containing T cell epitopes from Fel d 1, the major cat allergen, reduces allergic sensitization and improves surrogate markers of disease. Here, we demonstrate a key immunological mechanism, linked epitope suppression, associated with this therapeutic effect. Treatment with selected epitopes from a single allergen resulted in suppression of responses to other ("linked") epitopes within the same molecule. This phenomenon was induced after peptide immunotherapy in human asthmatic subjects and in a novel HLA-DR1 transgenic mouse model of asthma. Tracking of allergen-specific T cells using DR1 tetramers determined that suppression was associated with the induction of interleukin (IL)-10(+) T cells that were more abundant than T cells specific for the single-treatment peptide and was reversed by anti-IL-10 receptor administration. Resolution of airway pathophysiology in this model was associated with reduced recruitment, proliferation, and effector function of allergen-specific Th2 cells. Our results provide, for the first time, in vivo evidence of linked epitope suppression and IL-10 induction in both human allergic disease and a mouse model designed to closely mimic peptide therapy in humans.

Introduction: Bronchiolitis Obliterans Organising Pneumonia (BOOP) may often present initially as a recurrent spontaneous pneumothorax and then develop multi-system complications., Case Presentation: A 17-year-old boy presented with a pneumothorax, which developed into rapidly progressive Bronchiolitis Obliterans Organising Pneumonia (BOOP). He developed multi-organ dysfunction (including adult respiratory distress syndrome, oliguric renal failure, acute coronary syndrome, cardiac failure and a right atrial thrombus) which necessitated prolonged intensive care. Diagnosis was confirmed on open lung biopsy and he responded well to treatment with corticosteroids., Conclusion: BOOP is exquisitely sensitive to oral corticosteroids but if the diagnosis is not considered in such patients and appropriate treatment instituted early, BOOP may often lead to prolonged hospital admission with considerable morbidity.

Observational data suggest that periodic breathing is more common in subjects with low F(ETCO(2)), high apnoeic thresholds or high chemoreflex sensitivity. It is, however, difficult to determine the individual effect of each variable because they are intrinsically related. To distinguish the effect of isolated changes in chemoreflex sensitivity, mean F(ETCO(2)) and apnoeic threshold, we employed a modelling approach to break their obligatory in vivo interrelationship. We found that a change in mean CO(2) fraction from 0.035 to 0.045 increased loop gain by 70 +/- 0.083% (P < 0.0001), irrespective of chemoreflex gain or apnoea threshold. A 100% increase in the chemoreflex gain (from 800 l min(-1) (fraction CO(2))(-1)) resulted in an increase in loop gain of 275 +/- 6% (P < 0.0001) across a wide range of values of steady state CO(2) and apnoea thresholds. Increasing the apnoea threshold F(ETCO(2)) from 0.02 to 0.03 had no effect on system stability. Therefore, of the three variables the only two destabilizing factors were high gain and high mean CO(2); the apnoea threshold did not independently influence system stability. Although our results support the idea that high chemoreflex gain destabilizes ventilatory control, there are two additional potentially controversial findings. First, it is high (rather than low) mean CO(2) that favours instability. Second, high apnoea threshold itself does not create instability. Clinically the apnoea threshold appears important only because of its associations with the true determinants of stability: chemoreflex gain and mean CO(2).

Diaphragm paralysis may occur after traumatic phrenic nerve injury. Here we report three patients in whom right hemi-diaphragmatic paralysis developed after cardiac radiofrequency ablation. We hypothesise that local focused thermal energy at the time of the ablation may have caused direct neuronal damage by axonal coagulation necrosis. The prognosis for this type of injury may be reasonably good; two of the three patients fully recovered diaphragm function by 1 year.

In individuals with atopy and asthma, allergen-derived T cell peptides injected intradermally induce isolated late asthmatic reactions (LARs) followed by bronchial hyporesponsiveness to peptide, inhibition of the allergen-induced cutaneous late-phase reaction, and altered T cell function in vitro. Laboratory animal data indicate that "activation" and "tolerance" also occur if peptides are inhaled. In this study, we show that inhalation of Fel d 1-derived peptides induced isolated LAR in individuals with asthma sensitive to cat allergen comparable with that previously demonstrated using intradermal injection. LARs were accompanied by eosinophilia and nonsignificant elevations of total cysteinyl leukotrienes in the sputum. Unlike the intradermal route, repeated inhalation of peptides was not associated with abrogation of the LAR and produced a sputum eosinophilia comparable with the first exposure. In addition, there was no inhibition of the cutaneous late-phase reaction to whole cat dander. Thus, isolated LAR induced by inhaled, allergen-derived peptides represent a novel model of provoked asthma and are not associated with the induction of hyporesponsiveness ("tolerance") in the skin or lung.

Background: Some patients with asthma who are allergic to cats and are injected intradermally with short, overlapping, T-cell peptides derived from Fel d 1 develop late asthmatic reactions to the peptides, which are associated with a reduction in late-phase skin reactions induced by whole allergens and bronchial hyporesponsiveness to the peptides on the second injection. We aimed to ascertain the effect of multiple injections on the magnitude of the early and late phase skin reactions to intact allergens., Methods: After a 9-week run-in period, we randomly assigned patients with asthma and allergies to cats to receive either Fel d 1 peptides (90 microg in increasing divided doses) or placebo. The primary outcome was late-phase cutaneous reactions to whole cat dander. Outcomes were measured at baseline, 4-8 weeks, and 3-9 months. Analysis was by intention to treat., Findings: 16 patients were randomly assigned to the peptides, and eight to placebo. All patients completed the course of injections. Four of the 16 patients on Fel d 1 peptides had initial late asthmatic reactions, but could be desensitised to the higher dose of peptide. Patients in the peptide group but not the placebo group had a significant reduction in the size of their late reaction to whole cat dander between baseline and both follow-ups, but the difference between groups was not significant (first follow-up, difference -422.8 mm(2) [95% CI -1115.0 to 269.4], p=0.43; second follow-up -1180.8 mm(2) [-2216.8 to -144.8], p=0.058). The size of the late reaction to Fel d 1 significantly differed between treatment groups at both follow-ups. At second follow-up, the size of the early reaction to Fel D 1, but not to whole cat dander was significantly reduced in those on peptides compared with those on placebo. The concentration of interferon gamma and of interleukin 4 and 13, and the amount of proliferation, significantly decreased between baseline and second follow-up, and the concentration of interleukin 10 was significantly higher in patients on peptides, however, none of these values differed significantly between groups. Patients on peptides had a significantly greater decrease in the concentration of interferon gamma and interleukin 13, and in the amount of proliferation between baseline and first follow-up than did those on placebo., Interpretation: Several, short, overlapping Fel d 1 T-cell peptides have potential in treatment of cat allergy.

Allergen-derived peptides can induce T cell tolerance in naive and Ag-primed mice. This is preceded by transient T cell activation. In humans, intradermal administration of short allergen-derived T cell peptide epitopes provokes IgE-independent isolated late asthmatic reactions (LARs) in sensitized subjects. In this study, we determine whether, as in mouse models, such peptides produce hyporesponsiveness to rechallenge with peptides, or whole allergen, either clinically or in terms of in vitro T cell responses. We found that a second injection of cat allergen (Fel d 1)-derived T cell peptides was associated with a marked reduction, or absence, of the LAR, and that up to 40 wk was required for return to baseline values. The cutaneous late-phase reaction to whole cat dander was also inhibited, even in subjects who did not experience an initial LAR. These observations were associated with a significant decrease in peptide- and whole allergen-induced proliferation of PBMCs and the production of IL-4, IL-13, and IFN-gamma in cultures. Thus, allergen-derived peptides induce tolerance to subsequent peptide injection in the target organ (the lung), reduce late-phase cutaneous responsiveness to whole allergen, and alter in vitro T cell reactivity.

Short peptide sequences corresponding to T cell epitopes have been identified in the major cat allergen Fel d 1. In order to directly activate allergen-specific T cells in cat-allergic asthmatic individuals, peptides were administered by intradermal injection. Subsequently, a proportion of subjects experienced a delayed reduction of airway calibre manifested as a decrease in FEV(1). Changes in lung function occurred approximately 3 h after peptide injection, peaked at 6 h and resembled an isolated late asthmatic reaction (LAR). Using molecular tissue typing techniques, it was determined that many of the individuals experiencing isolated LAR expressed particular HLA-DR molecules. These molecules were shown in subsequent experiments to bind individual peptides within the preparation and thus to activate T cells in a major histocompatibility complex (MHC)-restricted fashion. The precise mechanisms whereby MHC-restricted activation of allergen-specific T cells gives rise to bronchoconstriction are currently under investigation., (Copyright 2001 S. Karger AG, Basel)

1. The effect of residence at altitude on the perception of breathlessness after return to sea level was examined in normal subjects. Breathlessness (Borg scale), minute ventilation, respiratory frequency, tidal volume, 'oxygen pulse' (oxygen consumption/heart rate) and the ventilatory equivalent for oxygen (minute ventilation/oxygen consumption) were measured at exercise (cycle-ergometer) during 5 months of training before 4 weeks at 4000 m and during the 6 month period after return to sea level. 2. There was no change in the subjects' pattern of breathing (respiratory frequency and tidal volume) or 'oxygen pulse' after the period at altitude (P = 0.0001). The ventilatory equivalent for oxygen was increased at all work rates after the period at altitude (P = 0.02). This ratio was slightly lower after 6 weeks and had returned to normal by 6 months (P = 0.4). 3. During training there was no change in breathlessness score (P = 0.6). On return to sea level, breathlessness score relative to ventilation was reduced (P = 0.0001). This was maintained for at least 6 weeks, but not as long as 6 months. 4. This study has demonstrated that, in normal subjects, the otherwise stable and reproducible relationship between breathlessness and ventilation may be disrupted for several weeks by factors other than lung disease. 5. The mechanism responsible for this is not clear, but the observations are consistent with the hypothesis that prior experience of breathlessness may condition subsequent estimates of breathlessness.