Research

The Role of Exercise in a Weight-Loss Program on Clinical Control in Obese Adults with Asthma. A Randomized Controlled Trial.

Am J Respir Crit Care Med. 2017 Jan 01;195(1):32-42

Authors: Freitas PD, Ferreira PG, Silva AG, Stelmach R, Carvalho-Pinto RM, Fernandes FL, Mancini MC, Sato MN, Martins MA, Carvalho CR

Abstract
RATIONALE: Clinical control is difficult to achieve in obese patients with asthma. Bariatric surgery has been recommended for weight loss and to improve asthma control; however, the benefits of nonsurgical interventions have been poorly investigated.
OBJECTIVES: To examine the effect of exercise training in a weight-loss program on asthma control, quality of life, inflammatory biomarkers, and lung function.
METHODS: Fifty-five obese patients with asthma were randomly assigned to either a weight-loss program plus exercise (WL + E group, n = 28) or a weight-loss program plus sham (WL + S group, n = 27), where the weight-loss program included nutrition (caloric restriction) and psychological therapies. The WL + E group incorporated aerobic and resistance muscle training, whereas the WL + S group incorporated breathing and stretching exercises.
MEASUREMENTS AND MAIN RESULTS: The primary outcome was clinical improvement in asthma control over 3 months. Secondary outcomes included quality of life, lung function, body composition, aerobic capacity, muscle strength, and inflammatory/antiinflammatory biomarkers. After 3 months, 51 patients were analyzed. Compared with the WL + S group, the WL + E group demonstrated improved clinical control scores (median [25th to 75th percentile], -0.7 [-1.3 to -0.3] vs. -0.3 [-0.9 to 0.4]; P = 0.01) and greater weight loss (mean ± SD, -6.8% ± 3.5 vs. -3.1% ± 2.6; P < 0.001) and aerobic capacity (median [25th to 75th percentile], 3.0 [2.4 to 4.0] vs. 0.9 [-0.3 to 1.3] ml O2 × kg(-1) × min(-1); P < 0.001). These improvements in the WL + E group were also accompanied by improvements in lung function, antiinflammatory biomarkers, and vitamin D levels, as well as reductions in airway and systemic inflammation.
CONCLUSIONS: Adding exercise to a short-term weight-loss program should be considered as a useful strategy for achieving clinical control of asthma in obese patients. Clinical trial registered with www.clinicaltrials.gov (NCT 02188940).

PMID: 27744739 [PubMed – indexed for MEDLINE]

Powered by WPeMatico

MHC class II deficiency: Report of a novel mutation and special review.

Allergol Immunopathol (Madr). 2017 Jul 01;:

Authors: Farrokhi S, Shabani M, Aryan Z, Zoghi S, Krolo A, Boztug K, Rezaei N

Abstract
The MHC II deficiency is a rare autosomal recessive primary immunodeficiency syndrome with increased susceptibility to respiratory and gastrointestinal infections, failure to thrive and early mortality. This syndrome is caused by mutations in transcription regulators of the MHC II gene and results in development of blind lymphocytes due to the lack of indicatory MHC II molecules. Despite homogeneity of clinical manifestations of patients with MHC II deficiency, the genetic defects underlying this disease are heterogeneous. Herein, we report an Iranian patient with MHC II deficiency harbouring a novel mutation in RFXANK and novel misleading clinical features. He had ataxic gait and dysarthria from 30 months of age. Epidemiology, clinical and immunological features, therapeutic options and prognosis of patients with MHC II are reviewed in this paper.

PMID: 28676232 [PubMed – as supplied by publisher]

Powered by WPeMatico

Primary Immunodeficiency Disorders in India-A Situational Review.

Front Immunol. 2017;8:714

Authors: Jindal AK, Pilania RK, Rawat A, Singh S

Abstract
Primary immunodeficiency disorders (PIDs) are a group of genetic defects characterized by abnormalities of one or more components of the immune system. While there have been several advances in diagnosis, management, and research in the field of PIDs, they continue to remain underdiagnosed, especially in the less affluent countries. Despite several limitations and challenges, India has advanced significantly in the field of PIDs in the last few years. In this review, we highlight the progress in the field of PIDs in India over the last 25 years, the difficulties faced by clinicians across the country, the current state of PIDs in India and the future prospects.

PMID: 28674536 [PubMed – in process]

Powered by WPeMatico

Recurrent and Sustained Viral Infections in Primary Immunodeficiencies.

Front Immunol. 2017;8:665

Authors: Ruffner MA, Sullivan KE, Henrickson SE

Abstract
Viral infections are commonplace and often innocuous. Nevertheless, within the population of patients with primary immunodeficiencies (PIDDs), viral infections can be the feature that drives a diagnostic evaluation or can be the most significant morbidity for the patient. This review is focused on the viral complications of PIDDs. It will focus on respiratory viruses, the most common type of viral infection in the general population. Children and adults with an increased frequency or severity of respiratory viral infections are often referred for an immunologic evaluation. The classic teaching is to investigate humoral function in people with recurrent sinopulmonary infections, but this is often interpreted to mean recurrent bacterial infections. Recurrent or very severe viral infections may also be a harbinger of a primary immunodeficiency as well. This review will also cover persistent cutaneous viral infections, systemic infections, central nervous system infections, and gastrointestinal infections. In each case, the specific viral infections may drive a diagnostic evaluation that is specific for that type of virus. This review also discusses the management of these infections, which can become problematic in patients with PIDDs.

PMID: 28674531 [PubMed – in process]

Powered by WPeMatico

Efficacy of mycophenolate on lung disease and autoimmunity in children with immunodeficiency.

Pediatr Pulmonol. 2017 Jul 03;:

Authors: Bucciol G, Petrone A, Putti MC

Abstract
The autoimmune manifestations of primary immunodeficiencies, such as autoimmune lymphoproliferative syndrome (ALPS) and common variable immunodeficiency (CVID), often constitute a great therapeutic challenge and have a significant impact on patients’ morbidity and mortality. The most common autoimmune presentations are autoimmune cytopenias, but organ-related autoimmunity is also frequently observed. From a pulmonology perspective, granulomatous/lymphocytic interstitial lung disease (GLILD) is a severe immunological complication which significantly worsens the clinical outcome of these patients and for which there are currently few guidelines or protocols for treatment. We present three cases where the use of Mycophenolate in the context of autoimmune cytopenias proved beneficial also on the lung disease.

PMID: 28672090 [PubMed – as supplied by publisher]

Powered by WPeMatico

Intrinsic and Extrinsic Causes of Malignancies in Primary Immunodeficiency Disorders.

J Allergy Clin Immunol. 2017 Jun 29;:

Authors: Hauck F, Voss R, Urban C, Seidel MG

Abstract
Malignancies occur with a higher incidence rate and manifest earlier in life in patients with primary immunodeficiency disorders (PID) than in the general population. However, no universal mechanism of malignancy predisposition in PID can been determined. Despite the strong support for the physiological role of tumor immunosurveillance and increasing success of strategies in immunological tumor therapy, which include checkpoint inhibition, monoclonal antibodies, and engineered T cell antigen receptors, the incidence and pattern of malignancies in PID do not reflect an increased tumor immune escape per se. In contrast, malignancies appear to be restricted to either i) tissue types bearing the same molecular defect that underlies the PID such as syndromes of DNA repair deficiency or immune cell-specific maturation or functional defects that suggest a cell-intrinsic oncogenic basis, or ii) other tissues when they are infected by transforming viruses or chronically inflamed, pointing towards extrinsic causes for transformation that are potentially facilitated by but not predominantly owed to a lack of immunosurveillance. Based on recent studies of preexisting conditions in malignancy patients and on malignancies in large PID cohorts, we conclude that a large part of tumor predisposition in PID is derived from the same molecular defect as the immunodeficiency itself. The presented concept elucidates diverse pathomechanisms and risks of malignancies in PID in the light of current tumor immune therapies.

PMID: 28669558 [PubMed – as supplied by publisher]

Powered by WPeMatico

Risks of serious infections in children treated with biologic response-modifying drugs: Bacterial infection risk in children with juvenile idiopathic arthritis.

Rheumatology (Oxford). 2017 Jun 27;:

Authors: Abinun M

PMID: 28666379 [PubMed – as supplied by publisher]

Powered by WPeMatico

Early-onset autoimmune disease due to a heterozygous loss-of-function mutation in TNFAIP3 (A20).

Ann Rheum Dis. 2017 Jun 28;:

Authors: Duncan CJA, Dinnigan E, Theobald R, Grainger A, Skelton AJ, Hussain R, Willet JDP, Swan DJ, Coxhead J, Thomas MF, Thomas J, Zamvar V, Slatter MA, Cant AJ, Engelhardt KR, Hambleton S

PMID: 28659290 [PubMed – as supplied by publisher]

Powered by WPeMatico

[Angioedema as initial manifestation of hypogammaglobulinemia].

Rev Alerg Mex. 2017 Apr-Jun;64(2):228-234

Authors: López-Rocha E, O’Farril-Romanillos P, Cerda-Reyes S, Medina-Torres EA, Espinosa-Padilla SE, Huerta-López JG, Blancas-Galicia L

Abstract
Common variable immunodeficiency is characterized by hypogammaglobulinemia and the inability to respond to vaccines. Patients mostly manifest infections, however only less than 5 % have pathological conditions as autoimmunity, granulomatous inflammation, and splenomegaly or lymphoproliferative disease among others, without showing infections. We report the case of a woman who debuted with localized cutaneous affection, facial angioedema, without other early symptoms. After diagnosis splenomegaly and bronchiectasis were documented. Angioedema and bronchiectasis responded with IVIG replacement. We also review the dermatological manifestations associated with CVID.

PMID: 28658731 [PubMed – in process]

Powered by WPeMatico

CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis.

N Engl J Med. 2017 Jun 28;:

Authors: Ozen A, Comrie WA, Ardy RC, Domínguez Conde C, Dalgic B, Beser ÖF, Morawski AR, Karakoc-Aydiner E, Tutar E, Baris S, Ozcay F, Serwas NK, Zhang Y, Matthews HF, Pittaluga S, Folio LR, Unlusoy Aksu A, McElwee JJ, Krolo A, Kiykim A, Baris Z, Gulsan M, Ogulur I, Snapper SB, Houwen RHJ, Leavis HL, Ertem D, Kain R, Sari S, Erkan T, Su HC, Boztug K, Lenardo MJ

Abstract
Background Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies. Methods We studied 11 patients with abdominal pain and diarrhea caused by early-onset protein-losing enteropathy with primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease; the disorder followed an autosomal recessive pattern of inheritance. Whole-exome sequencing was performed to identify gene variants. We evaluated the function of CD55 in patients’ cells, which we confirmed by means of exogenous induction of expression of CD55. Results We identified homozygous loss-of-function mutations in the gene encoding CD55 (decay-accelerating factor), which lead to loss of protein expression. Patients’ T lymphocytes showed increased complement activation causing surface deposition of complement and the generation of soluble C5a. Costimulatory function and cytokine modulation by CD55 were defective. Genetic reconstitution of CD55 or treatment with a complement-inhibitory therapeutic antibody reversed abnormal complement activation. Conclusions CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

PMID: 28657829 [PubMed – as supplied by publisher]

Powered by WPeMatico