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Monday, April 10, 2017

Effectiveness of bronchial thermoplasty in patients with severe refractory asthma: clinical and histopathological correlations

Asthma is a disease in which the airways of the lung become very sensitive to certain triggers, leading to spasms, in turn causing shortness of breath, coughing and wheezing.  The ultimate cause of asthma is unclear, but it has been shown in previous studies that there is remodeling of the airways in severe asthma. Airway smooth muscle (ASM) increases, along with fibrosis, infiltration of new blood vessels, and growth of cells that line the airways.   Recently, a procedure called bronchial thermoplasty (BT) has been developed, in which an endoscope is inserted into the airways.  This endoscope then delivers a temperature-controlled radio frequency to the airway wall.  In this month’s issue of JACI, Pretolani and colleagues look at bronchial thermoplasty and its effect on various clinical and histopathological findings (J Allergy Clin Immunol 2017; 139(4): 1176-1185).

In order to do this, they recruited 15 patients with severe uncontrolled asthma that did not respond to medications.  They looked at the symptoms through the Asthma Control Test (ACT) and the Asthma Quality of Life Questionnaire (AQLQ), as well as breathing patterns via spirometry and biopsy samples.  Bronchial thermoplasty was then performed.  At 3 and 12 months, the clinical and airway effects were examined.

What they found is that asthma control and quality of life increased considerably.  Exacerbations requiring oral steroids, emergency room visits, and hospitalizations were also decreased by approximately 90%.  Biopsy samples from 3 months showed a decrease in ASM size, as well as nerve fibers and neuroendocrine cells.

Based on these results, Pretolani and colleagues conclude that bronchial thermoplasty is an option for severe, uncontrolled, treatment refractory asthma.  Bronchial thermoplasty seems to affect the structure of airways, especially muscle size and nerve connections.  Targeting these structures, through thermoplasty or other means may be an effective way to help control these difficult-to-control cases.

Thursday, April 6, 2017

A prospective study on the natural history of patients with profound combined immunodeficiency (P-CID): an interim analysis

The immune system is complex, composed of numerous cells, proteins, and other components.  Among them, the T-cells are essential in fighting off infectious agents and regulating the functions of the immune system.  People with reduced or dysfunctional T-cells can have life-threatening complications, and may require interventions like hematopoietic stem cell transplant (HSCT), gene therapy, or enzyme replacement. If a T cell deficiency is severe (severe combined immunodeficiency, SCID), these treatment decisions are clear. However, in patients with moderate T cell deficiency (profound combined immunodeficiency, P-CID), prognosis is unclear and transplant decisions are difficult. These patients have so far received little attention.  In this month’s issue of JACI, Speckmann and colleagues report the first 51 P-CID patients  enrolled in a long-term prospective study (J Allergy Clin Immunol 2017; 139(4): 1302-1310). The patients suffer from heterogenous T cell deficiencies including: (1) ‘bona fide’ CID, where deficiencies are typically associated with profound T-cell deficiencie, (2) atypical severe combined immunodeficiency (SCID), in which T-cell dysfunction is due to less life-threatening mutations in SCID-associated genes, and (3) T cell deficiencies with genetically unidentified cause.  They analyzed  the clinical and molecular characteristics at study entry to determine disease severity.  Ultimately, the aim is to identify parameters predicting  when the risks of untreated disease outweigh the risks of performing HSCT.

They found that patients with P-CID have a high rate of morbidity and mortality as well as a lower quality of life.  One-third of patients underwent HSCT within the first year of inclusion into the study, 5 patients died.  The genetic diagnosis has limited value as a predictor of disease evolution and thus as a guidance for HSCT decisions, with the age of onset, quality of life, and severity of disease not significantly different between patients with atypical SCID, bona fide CVID, or genetically undefined disease.  This was in line with the authors’ expectations, but what they didn’t expect was that basic measures of T-cell immunity also did not predict the prognosis and course of their disease.

Speckmann and colleagues continue to enroll patients and hope to eventually reach their target of 120.  Parallel long-term follow-up of transplanted and of non-transplanted patients will better identify predictors for the natural progress of P-CID, and, in turn, give better guidance about how, and when, to treat with HSCT.