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.

Successful hematopoietic cell transplantation in a patient with X-linked agammaglobulinemia and acute myeloid leukemia.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in all classes of serum immunoglobulins and the near absence of mature CD19(+) B-cells. Although malignancy has been observed in patients with XLA, we present the first reported case of acute myeloid leukemia (AML) in a patient with XLA. We also demonstrate the complete correction of the XLA phenotype following allogeneic hematopoietic cell transplantation for treatment of the patient's leukemia.

Childhood obesity and asthma control in the GALA II and SAGE II studies.

RATIONALE: Obesity is associated with increased asthma morbidity, lower drug responsiveness to inhaled corticosteroids, and worse asthma control. However, most prior investigations on obesity and asthma control have not focused on pediatric populations, considered environmental exposures, or included minority children. OBJECTIVES: To examine the association between body mass index categories and asthma control among boys and girls; and whether these associations are modified by age and race/ethnicity. METHODS: Children and adolescents ages 8-19 years (n = 2,174) with asthma were recruited from the Genes-environments and Admixture in Latino Americans (GALA II) Study and the Study of African Americans, Asthma, Genes, and Environments (SAGE II). Ordinal logistic regression was used to estimate odds ratios (OR) and their confidence intervals (95% CI) for worse asthma control. MEASUREMENTS AND MAIN RESULTS: In adjusted analyses, boys who were obese had a 33% greater chance of having worse asthma control than their normal-weight counterparts (OR, 1.33; 95% CI, 1.04-1.71). However, for girls this association varied with race and ethnicity (P interaction = 0.008). When compared with their normal-weight counterparts, obese African American girls (OR, 0.65; 95% CI, 0.41-1.05) were more likely to have better controlled asthma, whereas Mexican American girls had a 1.91 (95% CI, 1.12-3.28) greater odds of worse asthma control. CONCLUSIONS: Worse asthma control is uniformly associated with increased body mass index in boys. Among girls, the direction of this association varied with race/ethnicity.

Factors associated with degree of atopy in Latino children in a nationwide pediatric sample: the Genes-environments and Admixture in Latino Asthmatics (GALA II) study.

BACKGROUND: Atopy varies by ethnicity, even within Latino groups. This variation might be due to environmental, sociocultural, or genetic factors. OBJECTIVE: We sought to examine risk factors for atopy within a nationwide study of US Latino children with and without asthma. METHODS: Aeroallergen skin test responses were analyzed in 1830 US Latino subjects. Key determinants of atopy included country/region of origin, generation in the United States, acculturation, genetic ancestry, and site to which subjects migrated. Serial multivariate zero-inflated negative binomial regressions stratified by asthma status examined the association of each key determinant variable with the number of positive skin test responses. In addition, the independent effect of each key variable was determined by including all key variables in the final models. RESULTS: In baseline analyses African ancestry was associated with 3 times (95% CI, 1.62-5.57) as many positive skin test responses in asthmatic participants and 3.26 times (95% CI, 1.02-10.39) as many positive skin test responses in control participants. Generation and recruitment site were also associated with atopy in crude models. In final models adjusted for key variables, asthmatic patients of Puerto Rican (exp[ß] [95% CI], 1.31 [1.02-1.69]) and mixed (exp[ß] [95% CI], 1.27 [1.03-1.56]) ethnicity had a greater probability of positive skin test responses compared with Mexican asthmatic patients. Ancestry associations were abrogated by recruitment site but not region of origin. CONCLUSIONS: Puerto Rican ethnicity and mixed origin were associated with degree of atopy within US Latino children with asthma. African ancestry was not associated with degree of atopy after adjusting for recruitment site. Local environment variation, represented by site, was associated with degree of sensitization.

Insect repellents and contact urticaria: differential response to DEET and picaridin.

Topical insect repellent is commonly used throughout the world. Active ingredients typically include N,N-diethyl-meta-toluamide (DEET) or picaridin. Reactions to topical repellents have ranged from contact dermatitis to urticaria. Exposure to DEET can produce contact urticaria; however, it is unknown if patients with a sensitivity to DEET can tolerate picaridin. We report the case of a 22-year-old man who presented for evaluation of contact urticaria that had developed immediately after the application of insect repellent and contact with individuals who had used DEET-containing repellents. No systemic manifestations were noted. Commercially available products containing DEET or picaridin were used for open patch testing. The patient showed immediate urticarial responses to 7% DEET and 7% DEET in ethanol, but patch tests for 5% picaridin and 5% picaridin in ethanol were negative. Based on these results, we conclude that insect repellents containing picaridin may be acceptable alternatives in patients who demonstrate sensitivity to products containing DEET.

Effect of secondhand smoke on asthma control among black and Latino children.

BACKGROUND: Among patients with asthma, the clinical effect and relative contribution of maternal smoking during pregnancy (in utero smoking) and current secondhand smoke (SHS) exposure on asthma control is poorly documented, and there is a paucity of research involving minority populations. OBJECTIVES: We sought to examine the association between poor asthma control and in utero smoking and current SHS exposure among Latino and black children with asthma. METHODS: We performed a case-only analysis of 2 multicenter case-control studies conducted from 2008-2010 with similar protocols. We recruited 2481 Latino and black subjects with asthma (ages 8-17 years) from the mainland United States and Puerto Rico. Ordinal logistic regression was used to estimate the effect of in utero smoking and current SHS exposures on National Heart, Lung, and Blood Institute-defined asthma control. RESULTS: Poor asthma control among children 8 to 17 years of age was independently associated with in utero smoking (odds ratio [OR], 1.5; 95% CI, 1.1-2.0). In utero smoking through the mother was also associated with secondary asthma outcomes, including early-onset asthma (OR, 1.7; 95% CI, 1.1-2.4), daytime symptoms (OR, 1.6; 95% CI, 1.1-2.1), and asthma-related limitation of activities (OR, 1.6; 95% CI, 1.2-2.2). CONCLUSIONS: Maternal smoking while in utero is associated with poor asthma control in black and Latino subjects assessed at 8-17 years of age.

ALOX5AP and LTA4H polymorphisms modify augmentation of bronchodilator responsiveness by leukotriene modifiers in Latinos.

BACKGROUND: Understanding the effects of interactions between multiple genes and asthma medications may aid in the understanding of the heterogeneous response to asthma therapies. OBJECTIVE: To identify modulating effects of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A(4) hydrolase (LTA4H) gene polymorphisms on the drug-drug interaction between leukotriene modifiers and albuterol in Mexicans and Puerto Ricans. METHODS: In a cross-sectional study of 293 Mexicans and 356 Puerto Ricans with asthma, ALOX5AP and LTA4H genes were sequenced, and interactions between gene polymorphisms and bronchodilator responsiveness to albuterol were compared between leukotriene modifier users and nonusers. RESULTS: In heterozygotes and homozygotes for the minor allele at LTA4H single nucleotide polymorphism (SNP) rs2540491 and heterozygotes for the major allele at LTA4H SNP rs2540487, leukotriene modifier use was associated with a clinically significant increase in percent change in FEV(1) after albuterol administration of 7.10% (P = .002), 10.06% (P = .001), and 10.03% (P < .001), respectively. Presence of the major allele at ALOX5AP SNP rs10507391 or the minor allele at ALOX5AP SNP rs9551963 augmented this response. When stratified by ethnicity, these findings held true for Puerto Ricans but not Mexicans. CONCLUSION: LTA4H and ALOX5AP gene polymorphisms modify the augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not Mexicans with asthma.

Clinical Observation of COVID-19 in a Patient With an Acquired Humoral Deficiency Secondary to Chemotherapeutic Agents.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes worldwide devastation. We describe the course of a patient with COVID-19 in the setting of an acquired humoral deficiency as a result of chemotherapeutic treatment for rheumatologic conditions. CASE REPORT: A 49-year-old Caucasian male presented with non-relieving fever, hypoxemia, and persistent diarrhea after seven days following a positive SARS-CoV-2 polymerase chain reaction (PCR) assay. The patient's past medical history was significant for mixed connective tissue disease, rheumatoid arthritis, and systemic lupus erythematosus treated with methotrexate and rituximab since 2008. He was diagnosed with acquired humoral deficiency in 2017 managed by intravenous immunoglobulin (IVIG) infusion every three weeks. The patient's course of hospitalization was complicated by acute respiratory distress which necessitated intensive unit care and required up to 20 L/min oxygen supplementation via a humidified high flow generator. He was treated with hydroxychloroquine and azithromycin and received an IVIG transfusion. The patient was discharged to home after forty-two days of hospitalization with oxygen supplementation only during ambulation and a complete resolution of diarrhea. DISCUSSION: According to current limited data, patients with immunodeficiency have longer length of hospitalization compared to immunocompetent individuals. Our patient demonstrated a form of immunodeficiency as the result of a chemotherapeutic agent, and his clinical course appeared to be more severe. CONCLUSION: More studies are necessary to shed light on the immunological response to SARS-CoV-2 and its impact on immunocompromised and immunocompetent and individuals. We describe the course of a patient with COVID-19 in the setting of an acquired humoral deficiency.

Persistent systemic inflammation and atypical enterocolitis in patients with NEMO syndrome.

The NEMO syndrome is a primary immunodeficiency with immune and non-immune manifestations. The immune deficiency is heterogeneous showing defects in humoral, innate, and cell-mediated immunity. While the clinical aspects of the immunodeficiency are increasingly well understood, little is known about autoimmune manifestations in NEMO patients. We therefore sought to examine serologic markers of systemic inflammation and intestinal pathology in a kindred of patients with the NEMO syndrome. We observed persistent elevation of erythrocyte sedimentation rates in five patients, and two were symptomatic, with a chronic but atypical enterocolitis. Though pathologic lesions in these two patients were consistent with acute inflammation, sustained clinical improvement was only achieved with systemic and/or topical glucocorticoid therapy. Our data suggest that some patients with the NEMO syndrome exhibit persistent elevation of inflammatory markers similar to systemic autoimmune diseases and may subsequently develop an atypical enterocolitis.