Association between α1-antitrypsin and bronchiectasis in patients with humoral immunodeficiency receiving gammaglobulin infusions.

BACKGROUND: In patients with humoral immunodeficiency, the progression of bronchiectasis has been known to occur despite adequate gammaglobulin therapy and in the absence of recurrent infections. This observation suggests that factors other than gammaglobulin replacement might play a part in the prevention of lung damage in this population. α1-Antitrypsin deficiency can be associated with bronchiectasis, a chronic inflammatory lung disease. The protective levels of α1-antitrypsin and phenotype in preventing bronchiectasis have not been thoroughly studied in the immunodeficient population. We hypothesized that patients with humoral immunodeficiencies on gammaglobulin infusions and bronchiectasis have lower median levels, but not necessary "classically" deficient levels, of α1-antitrypsin compared with those without bronchiectasis. OBJECTIVE: To compare levels of α1-antitrypsin in subjects with immunodeficiency with and without bronchiectasis. METHODS: One hundred ninety-two subjects with humoral immunodeficiencies requiring gammaglobulin therapy had their α1-antitrypsin levels and phenotype screened. High-resolution computed tomograms of the chest of participants were obtained and compared with α1-antitrypsin levels and phenotype. RESULTS: Participants without bronchiectasis were found to have higher median levels of α1-antitrypsin than those with bronchiectasis (P = .003). Furthermore, subjects with improving or resolved bronchiectasis since initiating gammaglobulin therapy had higher median levels of α1-antitrypsin than those with worsening bronchiectasis (P = .004). The prevalence of the α1-antitrypsin PiZZ mutation was higher than in the general public (P < .0001). CONCLUSION: Median α1-antitrypsin levels and phenotype in subjects were associated with humoral immunodeficiency and their bronchiectasis status. Prospective studies might be necessary to determine possible benefits of augmentation therapy. This study supports the idea that what is considered a "normal or protective" α1-antitrypsin range might need to be refined for patients with humoral immunodeficiency on gammaglobulin therapy.

Differential effects of obesity on eosinophilic vs. non-eosinophilic asthma subtypes.

OBJECTIVE: Asthma is a heterogeneous disease composed of multiple disease subtypes. Obesity may worsen asthma, although the mechanism is poorly understood and its effects on different subtypes are not well characterized. We sought to determine whether obesity affects eosinophilic asthma differently from non-eosinophilic asthma. METHODS: Charts of 196 persistent asthmatics were reviewed. Subjects were categorized according to BMI (obese ≥ 30 kg/m2) and blood eosinophilia based on two different cutoffs (≥200 or ≥400 cells/µl): eosinophilic, non-obese (E-NO), eosinophilic, obese (E-O), non-eosinophilic, non-obese (NE-NO), and non-eosinophilic, obese (NE-O). We analyzed clinical parameters across these groups to determine associations with obesity and/or eosinophilia. RESULTS: Obesity was highly prevalent in our population (50.5%, 99/196). The majority of asthmatics were female (75.5%), though the ratio was lower in the E-NO group (56%). The NE-NO group was associated with lowest asthma severity, lower atopy, and less medication use. Regardless of eosinophilia, obesity was associated with higher inhaled corticosteroid doses and lower FVC% predicted than their non-obese counterparts. Obesity was associated with reduced FEV1% only in the non-eosinophilic group. Eosinophilia was also associated with reduced FEV1% in the non-obese subjects, but FEV1% was not further reduced in the E-O group compared to the E-NO and NE-O groups. Similar findings were observed regardless of whether the blood eosinophil cutoff was 200 or 400 cells/ µl. CONCLUSION: Multiple clinical features of asthma are adversely affected by obesity, which may affect eosinophilic and non-eosinophilic subtypes differently.

Childhood Polyarthritis As Early Manifestation of Autoimmune Polyendocrinopathy with Candidiasis and Ectodermal Dystrophy Syndrome.

Autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED) is a rare disorder of immune dysregulation caused by mutations in the autoimmune regulator (AIRE) gene. Individuals affected with APECED develop a clinical syndrome characterized by ectodermal abnormalities, autoantibody production, and organ-specific autoimmune manifestations. Inflammatory arthritis is usually not described as a part of the syndrome, and only sporadic cases are reported. We describe the case of a preschool-age girl who presented with hypoparathyroidism, hepatitis, interstitial pneumonitis, and chronic polyarthritis at 4 years of age and was found to have two compound heterozygous disease-associated mutations in the AIRE gene. We also conducted a literature review of the main characteristics of inflammatory arthritis in APECED patients. Our case and review demonstrate that (1) inflammatory arthritis, although rare, can be an early manifestation of APECED; (2) the diagnosis of APECED should be considered if mucocutaneous candidiasis, multiple organ-specific autoimmune manifestations, polyendocrinopathy, especially hypoparathyroidism or adrenal failure, or ectodermal dystrophy accompany joint symptoms; and (3) genotyping interpretation should take into account that mutations are found in the 14 exons of the gene, compound heterozygosity is common, and in some cases, only one or no mutated alleles are found.

Review of Select Practice Parameters, Evidence-Based Treatment Algorithms, and International Guidelines for Hereditary Angioedema.

Hereditary angioedema (HAE) is a rare bradykinin-mediated disease that is characterized by recurrent attacks of subcutaneous or submucosal edema, which can be life threatening. HAE affects all ethnic groups equally and does not differentiate between age, sex, or race. However, the availability of therapies varies amongst countries resulting in a lack of uniformity of care. Not only is there a disparity of medication availability, but since HAE is a rare disease, it is frequently overlooked and the diagnosis is missed. Even with diagnosis, treatment and management is often less than optimal. For these reasons, it is essential to have practice parameters and guidelines. In this chapter, we focus on recent guidelines. These guidelines deal with recognition, diagnosis, medical care, patient management, and assessment, all which are essential to provide optimal care to people with a rare and orphan disease. The intent of the guidelines, and thus this chapter, is to reduce morbidity and mortality, and restore a normal quality of life for the patient with HAE. We will review the guidelines from various regions of the world as well as international group recommendations. In addition, specific patient populations such as the pregnant, elderly, and juvenile require modified treatment regimens, and for this reason, we have included these data as well. The intent of this chapter is to aid the practitioner in holistic care of the patient with HAE in order to ultimately provide the best standard of care possible.