Research

Clinical characteristics and etiologies of bronchiectasis in Korean children: A multicenter retrospective study.

Respir Med. 2019 Apr;150:8-14

Authors: Lee E, Shim JY, Kim HY, Suh DI, Choi YJ, Han MY, Baek KS, Kwon JW, Cho J, Jung M, Kim YS, Sol IS, Kim BS, Chung EH, Lee S, Jeong K, Jang YY, Jang GC, Hyun MC, Yang HJ, Shin M, Kim JT, Kim JH, Hwang YH, Ahn JY, Seo JH, Jung JA, Kim HS, Oh MY, Park Y, Lee MH, Lee SY, Jung S, Hong SJ, Ahn YM, on the behalf of Pediatric Respiratory and Diseases Study Party

Abstract
BACKGROUND: Bronchiectasis is a chronic pulmonary disease characterized by progressive and irreversible bronchial dilatation. The aim of the present study was to investigate the etiologies and clinical features of bronchiectasis in Korean children.
METHODS: We performed a retrospective review of the medical records for children diagnosed with bronchiectasis between 2000 and 2017 at 28 secondary or tertiary hospitals in South Korea.
RESULTS: A total of 387 cases were enrolled. The mean age at diagnosis was 9.2 ± 5.1 years and 53.5% of the patients were boys. The most common underlying cause of bronchiectasis was preexisting respiratory infection (55.3%), post-infectious bronchiolitis obliterans (14.3%), pulmonary tuberculosis (12.3%), and heart diseases (5.6%). Common initial presenting symptoms included chronic cough (68.0%), recurrent pneumonia (36.4%), fever (31.1%), and dyspnea (19.7%). The most predominantly involved lesions were left lower lobe (53.9%), right lower lobe (47.1%) and right middle lobe (40.2%). No significant difference was observed in the distribution of these involved lesions by etiology. The forced expiratory volume in 1 s (FEV1) levels were lowest in cases with interstitial lung disease-associated bronchiectasis, followed by those with recurrent aspiration and primary immunodeficiency.
CONCLUSIONS: Bronchiectasis should be strongly considered in children with chronic cough and recurrent pneumonia. Long-term follow-up studies on pediatric bronchiectasis are needed to further clarify the prognosis and reduce the disease burden in these patients.

PMID: 30961955 [PubMed – in process]

Powered by WPeMatico

Autoimmune Lymphoproliferative Syndrome: An Overview.

Arch Pathol Lab Med. 2019 Apr 08;:

Authors: Matson DR, Yang DT

Abstract
Autoimmune lymphoproliferative syndrome (ALPS) is an inherited nonmalignant lymphoproliferative disorder characterized by heterozygous mutations within the first apoptosis signal receptor (FAS) signaling pathway. Defects in FAS-mediated apoptosis cause an expansion and accumulation of autoreactive CD4- and CD8- (double-negative) T cells, leading to cytopenias, splenomegaly, lymphadenopathy, autoimmune disorders, and a greatly increased lifetime risk of lymphoma. The differential diagnosis of ALPS includes infection, other inherited immunodeficiency disorders, primary and secondary autoimmune syndromes, and lymphoma. The most consistent pathologic feature is a florid paracortical expansion of double-negative T cells in lymph nodes. A presumptive clinical diagnosis can be made from symptoms and a constellation of laboratory test results. However, a definitive diagnosis requires ancillary testing and enables disease subclassification. Recognition of ALPS is critical, as treatment with immunosuppressive therapies can effectively reduce or ameliorate symptoms for most patients.

PMID: 30958694 [PubMed – as supplied by publisher]

Powered by WPeMatico

[Common variable immune deficiency in adults: focus on pulmonary complications].

Ter Arkh. 2017;89(12. Vyp. 2):211-215

Authors: Fomina DS, Bobrikova EN, Sinyavkin DO, Parshin VV

Abstract
Common variable immune deficiency is the most common form of a group of primary immunodeficiencies in adult patients. Pulmonary complications occupy leading positions. It is the development of recurrent bronchopulmonary inflammatory diseases that is considered to be one of the main causes of death and disability in patients with this disease. By presenting two clinical cases with long diagnostic delays, the authors try to attract the attention of specialists of related professions, which will minimize the development of irreversible complications in the patients.

PMID: 29488483 [PubMed – indexed for MEDLINE]

Powered by WPeMatico

Population pharmacokinetic modeling and simulation of immunoglobulin exposure with varying dosing intervals of subcutaneous immunoglobulin 20% (Ig20Gly) in patients with primary immunodeficiency diseases.

Int Immunopharmacol. 2019 Apr 02;71:404-410

Authors: Dumas T, Berry NS, Wolfsegger M, Jolles S, McCoy B, Yel L

Abstract
BACKGROUND: Immunoglobulin (IG) replacement therapy in patients with primary immunodeficiency diseases (PID) can be administered daily to every 2 weeks subcutaneously (SCIG) or every 3 or 4 weeks intravenously (IVIG).
OBJECTIVES: Develop a population pharmacokinetic (PK) model simulating IG exposure with Ig20Gly, a 20% SCIG; determine the dose adjustment factor for Ig20Gly relative to IVIG.
METHODS: Data from patients with PID treated with Ig20Gly and IVIG 10% were used to characterize IG population PK by nonlinear mixed-effects modeling and validated using data splitting and a visual predictive check. IG profiles were simulated for 1000 patients/interval treated with Ig20Gly (daily, every 2 days, every 3 days, twice weekly, weekly, every 2 weeks). An Ig20Gly adjustment factor of 130% was used to simulate Ig20Gly to IVIG AUC ratios for weekly or every 2 weeks Ig20Gly dosing intervals and a monthly IVIG dosing interval.
RESULTS: A 1-compartment model, using weight as a covariate on clearance, derived from an index modeling dataset (n = 81) demonstrated predictability for a validation dataset (n = 21). The model estimate of bioavailability was 73.9%. Simulations for 6 dosing intervals showed similar mean profiles with overlapping prediction intervals. Mean AUC ratios of Ig20Gly to IVIG with a dose adjustment factor of 1.30:1 were 98.7% for weekly and 97.7% for twice-weekly administration demonstrating comparable exposure.
CONCLUSION: Ig20Gly exposures from daily to up to every 2 weeks appeared equivalent. A 1.30 conversion factor provided coverage comparable to IVIG when Ig20Gly is administered daily to every 2 weeks.

PMID: 30952104 [PubMed – as supplied by publisher]

Powered by WPeMatico

Successful liver transplantation in common variable immune deficiency with reversal of hepatopulmonary syndrome.

BMJ Case Rep. 2019 Apr 03;12(4):

Authors: Apostolov R, Sinclair M, Lokan J, Angus P

Abstract
Common variable immune deficiency (CVID) is a primary immunodeficiency disorder that is associated with abnormal liver function tests, however advanced liver disease is uncommon. Hepatopulmonary syndrome (HPS) is a rare but debilitating complication of CVID-associated liver disease. We report a case of CVID complicated by HPS that was successfully treated with orthotopic liver transplant, with the patient recovering to normal hepatic function and successfully weaning off domiciliary oxygen post-transplantation.

PMID: 30948390 [PubMed – in process]

Powered by WPeMatico

Severe Facial Herpes Vegetans and Viremia in NFKB2-Deficient Common Variable Immunodeficiency.

Front Pediatr. 2019;7:61

Authors: Parsons K, Cipriano SD, Rosen LB, Browne SK, Walter JE, Stone BL, Keeshin S, Chen K

Abstract
With the accessibility of next-generation sequencing modalities, an increasing number of primary immunodeficiency disorders (PIDDs) such as common variable immunodeficiency (CVID) have gained improved understanding of molecular pathogenesis and disease phenotype with the identification of a genetic etiology. We report a patient with early-onset CVID due to an autosomal dominant loss-of-function mutation in NFKB2 who developed a severe herpes vegetans cutaneous infection as well as concurrent herpes simplex virus viremia. The case highlights features of CVID, unique aspects of NF-κB2 deficiency including susceptibility to herpesvirus infections, the detection of neutralizing anticytokine antibodies, and the complexity of medical management of patients with a PIDD that can be aided by a known genetic diagnosis.

PMID: 30941333 [PubMed]

Powered by WPeMatico

Clinical and Immunological Phenotype of Patients With Primary Immunodeficiency Due to Damaging Mutations in NFKB2.

Front Immunol. 2019;10:297

Authors: Klemann C, Camacho-Ordonez N, Yang L, Eskandarian Z, Rojas-Restrepo JL, Frede N, Bulashevska A, Heeg M, Al-Ddafari MS, Premm J, Seidl M, Ammann S, Sherkat R, Radhakrishnan N, Warnatz K, Unger S, Kobbe R, Hüfner A, Leahy TR, Ip W, Burns SO, Fliegauf M, Grimbacher B

Abstract
Non-canonical NF-κB-pathway signaling is integral in immunoregulation. Heterozygous mutations in NFKB2 have recently been established as a molecular cause of common variable immunodeficiency (CVID) and DAVID-syndrome, a rare condition combining deficiency of anterior pituitary hormone with CVID. Here, we investigate 15 previously unreported patients with primary immunodeficiency (PID) from eleven unrelated families with heterozygous NFKB2-mutations including eight patients with the common p.Arg853* nonsense mutation and five patients harboring unique novel C-terminal truncating mutations. In addition, we describe the clinical phenotype of two patients with proximal truncating mutations. Cohort analysis extended to all 35 previously published NFKB2-cases revealed occurrence of early-onset PID in 46/50 patients (mean age of onset 5.9 years, median 4.0 years). ACTH-deficiency occurred in 44%. Three mutation carriers have deceased, four developed malignancies. Only two mutation carriers were clinically asymptomatic. In contrast to typical CVID, most patients suffered from early-onset and severe disease manifestations, including clinical signs of T cell dysfunction e.g., chronic-viral or opportunistic infections. In addition, 80% of patients suffered from (predominately T cell mediated) autoimmune (AI) phenomena (alopecia > various lymphocytic organ-infiltration > diarrhea > arthritis > AI-cytopenia). Unlike in other forms of CVID, auto-antibodies or lymphoproliferation were not common hallmarks of disease. Immunophenotyping showed largely normal or even increased quantities of naïve and memory CD4+ or CD8+ T-cells and normal T-cell proliferation. NK-cell number and function were also normal. In contrast, impaired B-cell differentiation and hypogammaglobinemia were consistent features of NFKB2-associated disease. In addition, an array of lymphocyte subpopulations, such as regulatory T cell, Th17-, cTFH-, NKT-, and MAIT-cell numbers were decreased. We conclude that heterozygous damaging mutations in NFKB2 represent a distinct PID entity exceeding the usual clinical spectrum of CVID. Impairment of the non-canonical NF-κB pathways affects function and differentiation of numerous lymphocyte-subpopulations and thus causes a heterogeneous, more severe form of PID phenotype with early-onset. Further characteristic features are multifaceted, primarily T cell-mediated autoimmunity, such as alopecia, lymphocytic organ infiltration, and in addition frequently ACTH-deficiency.

PMID: 30941118 [PubMed – in process]

Powered by WPeMatico