Feasibility of a nasal breathing training during pulmonary rehabilitation. A pilot randomized controlled study.

Hyperventilation syndrome (HVS) is a common source of dyspnea and disability. While pulmonary rehabilitation (PR) including breathing exercises is indicated, randomized controlled trial are warranted to recommend one type of breathing exercise than another. We aimed to compare during PR, the effect of 5 sessions of nasal ventilation exercise (NV+PR) versus voluntary hypoventilation (vHV+PR) on exercise dyspnea (primary outcome) and capacity and health-related quality of life in patients. In this open label randomized controlled trial, 19 HVS patients (age=48.3 ± 15.2 y.o, female/male=18/1, Nijmegen score=33 ± 7.7) were randomized in a NV+PR (n = 9) or vHV+PR (n = 10) group. Modified Medical Research Council (mMRC) dyspnea, 6-minute walking distance (6MWD) with nasal/oral ventilation were assessed before and after 3 months of PR, and questionnaires (Nijmegen, VQ-11). There was a significant effect of PR of but no significant difference between groups in the improvements of dyspnea@max exercise (time effect (T): p < 0.01; group (G): p = 0.63; group*time interaction (G*T): p = 0.49), mMRC dyspnea (T: p < 0.01; G: p = 0.45; G*T: p = 0.62), 6MWD (T: p < 0.05; G: p = 0.36; G*T: p = 0.31), VQ-11 (T: p < 0.001; G: p = 0.16; G*T: p = 0.09) and plasma HCO3- (T: p < 0.05; G: p = 0.93; G*T; p = 0.36), Yet, Nijmegen score (T: p < 0.01; G: p = 0.32; G*T: p < 0.05) improvement was larger in NV+PR group. The exercise oronasal breathing shift during the 6MWT was significantly delayed in all patients (T: p < 0.05; G: p = 0.30; G*T: p = 0.32) and positively correlated with plasma HCO3-(r = 0.42; p < 0.05). Nasal exercise was not superior versus voluntary hypoventilation during PR in HVS patients. Yet, nasal exercise appeared feasible, leading to acquisition of a nasal breathing pattern during walking, improvement of PR outcomes and ventilatory alkalosis. The link between nasal breathing and hyperventilation is discussed in the light of the nasal ventilation rhythm in the limbic system and its role on the limbic emotional and ventilatory functions.

[Granulomatous lung disease induced by kayexalate inhalation during immunotherapy for metastatic melanoma]. / Pneumopathie granulomateuse induite par l'inhalation de Kayexalate® sous immunothérapie: Un diagnostic différentiel de progression tumorale et de toxicité pulmonaire spécifique des inhibiteurs de checkpoints immunitaires.

INTRODUCTION: When a patient treated by immune checkpoint inhibitors for metastatic melanoma presents with pulmonary symptoms, several diagnoses are possible. We report a case of acute granulomatous lung disease secondary to repeated kayexalate inhalations, and probably stimulated by immunotherapy. CASE REPORT: A patient treated with pembrolizumab and then ipilimumab presented with fever and acute shortness of breath. His pulmonary symptoms got progressively worse, leading to an acute respiratory distress syndrome. Chest CT displayed a pattern of non-specific organized pneumonia. Pulmonary infection, tumor progression, specific immune-related lung toxicity and immunotherapy-induced sarcoidosis were discussed. Histopathological examination of a lung biopsy showed a foreign body granulomatous macrophage reaction associated with crystalline, basophilic, purple and laminated elements, evoking kayexalate particles. These elements helped rewrite the diagnosis and confirmed a kayexalate-induced granulomatous lung disease secondary to repeated aspiration. The patient's respiratory condition got better following discontinuation of kayexalate together with systemic corticosteroids. Symptoms relapsed with resumption of the immunotherapy but were controlled with the addition of a new course of prolonged systemic corticosteroid therapy. We can hypothesize that immunotherapy played a role in the recurrence of the granulomatous lung reaction, or that there was an association between an aspiration pneumonia and an immunotherapy-induced lung toxicity. CONCLUSION: Facing respiratory symptoms during immunotherapy, the treatment may be the cause, but lung biopsy should be performed rapidly to arrive to a certain diagnosis.

Photograph-based diagnosis of burns in patients with dark-skin types: the importance of case and assessor characteristics.

AIM: This study assessed whether photographs of burns on patients with dark-skin types could be used for accurate diagnosing and if the accuracy was affected by physicians' clinical background or case characteristics. METHOD: 21 South-African cases (Fitzpatrick grades 4-6) of varying complexity were photographed using a camera phone and uploaded on a web-survey. Respondents were asked to assess wound depth (3 categories) and size (in percentage). A sample of 24 burn surgeons and emergency physicians was recruited in South-Africa, USA and Sweden. Measurements of accuracy (using percentage agreement with bedside diagnosis), inter- (n=24), and intra-rater (n=6) reliability (using percentage agreement and kappa) were computed for all cases aggregated and by case characteristic. RESULTS: Overall diagnostic accuracy was 67.5% and 66.0% for burn size and depth, respectively. It was comparable between burn surgeons and emergency physicians and between countries of practice. However, the standard deviations were smaller, showing higher similarities in diagnoses for burn surgeons and South-African clinicians compared to emergency physicians and clinicians from other countries. Case characteristics (child/adult, simple/complex wound, partial/full thickness) affected the results for burn size but not for depth. Inter- and intra-rater reliability for burn depth was 55% and 77%. CONCLUSION: Size and depth of burns on patients with dark-skin types could be assessed at least as well using photographs as at bedside with 67.5% and 66.0% average accuracy rates. Case characteristics significantly affected the accuracy for burn size, but medical specialty and country of practice seldom did in a statistically significant manner.

X-linked CHARGE-like Abruzzo-Erickson syndrome and classic cleft palate with ankyloglossia result from TBX22 splicing mutations.

X-linked cleft palate (CPX) is caused by mutations in the gene encoding the TBX22 transcription factor and is known to exhibit phenotypic variability, usually involving either a complete, partial or submucous cleft palate, with or without ankyloglossia. This study hypothesized a possible involvement of TBX22 in a family with X-linked, CHARGE-like Abruzzo-Erickson syndrome, of unknown etiology. The phenotype extends to additional features including sensorineural deafness and coloboma, which are suggested by the Tbx22 developmental expression pattern but not previously associated in CPX patients. A novel TBX22 splice acceptor mutation (c.593-5T>A) was identified that tracked with the phenotype in this family. A novel splice donor variant (c.767+5G>A) and a known canonical splice donor mutation (c.767+1G>A) affecting the same exon were identified in patients with classic CPX phenotypes and were comparatively analyzed using both in silico and in vitro splicing studies. All three variants were predicted to abolish normal mRNA splicing and an in vitro assay indicated that use of alternative splice sites was a likely outcome. Collectively, the data showed the functional effect of several novel intronic splice site variants but most importantly confirms that TBX22 is the gene underlying Abruzzo-Erickson syndrome, expanding the phenotypic spectrum of TBX22 mutations.