Serum IgG and risk of exacerbations and hospitalizations in chronic obstructive pulmonary disease

Filho, Fernando Sergio Leitão; Won, Seung; Mattman, André; Schellenberg, Robert; Fishbane, Nick; Criner, Gerard J.; Woodruff, Prescott G.; Lazarus, Stephen C.; Albert, Richard K.; Connett, John E.; Han, MeiLan K.; Martínez, Fernando J.; Leung, Janice M.; Man, S. F. Paul; Aaron, Shawn D.; Reed, Robert M.; Sin, Don D.

doi:10.1016/j.jaci.2017.01.046

Cited by 35 publications

(30 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to its association with autoimmune diseases, cigarette smoke is the main risk factor for COPD . In this context, others have shown that about 25% of COPD patients have total serum IgG levels below the lower limit of normal, consistent with our findings in smokers without COPD. This is associated with an increased incidence of exacerbations and hospitalizations (usually because of respiratory tract infections), and this is mainly in patients with deficiencies in IgG1 and/or IgG2 subclasses .…”

Section: Discussionsupporting

confidence: 92%

Cigarette smoking differentially affects immunoglobulin class levels in serum and saliva: An investigation and review

Tarbiah

Todd

Tighe

et al. 2019

Basic Clin Pharma Tox

View full text Add to dashboard Cite

The aim of the present study was to compare concentrations of IgG, IgA, IgM and IgD in both serum and saliva samples from smoking and non‐smoking individuals using a protein microarray assay. The findings were also compared to previous studies. Serum and saliva were collected from 48 smoking male individuals and 48 age‐matched never‐smoker male individuals. The protein microarray assays for detection of human IgG, IgM, IgA and IgD were established and optimized using Ig class‐specific affinity‐purified goat anti‐human Ig‐Fc capture antibodies and horseradish peroxidase (HRP)‐conjugated goat anti‐human Ig‐Fc detection antibodies. The Ig class specificity of the microarray assays was verified, and the optimal dilutions of serum and saliva samples were determined for quantification of Ig levels against standard curves. We found that smoking is associated with reduced IgG concentrations and enhanced IgA concentrations in both serum and saliva. By contrast, smoking differentially affected IgM concentrations—causing increased concentrations in serum, but decreased concentrations in saliva. Smoking was associated with decreased IgD concentrations in serum and did not have a significant effect on the very low IgD concentrations in saliva. Thus, cigarette smoking differentially affects the levels of Ig classes systemically and in the oral mucosa. Although there is variation between the results of different published studies, there is a consensus that smokers have significantly reduced levels of IgG in both serum and saliva. A functional antibody deficiency associated with smoking may compromise the body's response to infection and result in a predisposition to the development of autoimmunity.

show abstract

Section: Discussionsupporting

confidence: 92%

Cigarette smoking differentially affects immunoglobulin class levels in serum and saliva: An investigation and review

Tarbiah

Todd

Tighe

et al. 2019

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

“…There is also some evidence that antibody deficiency may be a treatable underlying contributor in other airway diseases. For example, low circulating IgG levels are associated with higher rate of exacerbations and shorter time to next exacerbation in two COPD cohorts . Treatment with immunoglobulin replacement is associated with significant reduction in exacerbations and rescue antibiotic use in a small case series of 14 COPD patients (: References S8), warranting future prospective, randomized clinical trials to assess the efficacy of IVIG in preventing exacerbations in selected COPD patients with antibody deficiency.…”

Section: Impaired Airway Mucosal Defencementioning

confidence: 99%

Precision medicine in united airways disease: A “treatable traits” approach

Yii

Tay

Choo

et al. 2018

Allergy

View full text Add to dashboard Cite

United airways disease (UAD) is the concept that the upper and lower airways, which are anatomically and immunologically related, form a single organ. According to this concept, upper and lower airway diseases are frequently comorbid because they reflect manifestations of a single underlying disease at different sites of the respiratory tract. Allergic asthma-allergic rhinitis is the archetypal UAD, but emerging data indicate that UAD is a heterogeneous condition and consists of multiple phenotypes (observable clinical characteristics) and endotypes (pathobiologic mechanisms). The UAD paradigm also extends to myriad sinonasal diseases (eg, chronic rhinosinusitis with or without nasal polyps) and lower airway diseases (eg, bronchiectasis, chronic obstructive pulmonary disease). Here, we review currently known phenoendotypes of UAD and propose a "treatable traits" approach for the classification and management of UAD, wherein pathophysiological mechanisms and factors contributing to disease are identified and targeted for treatment. Treatable traits in UAD can be analyzed according to a framework comprising airway inflammation (eosinophilic, neutrophilic), impaired airway mucosal defense (impaired mucociliary clearance, antibody deficiency), and exogenous cofactors (allergic sensitizers, tobacco smoke, microbes). Appreciation of treatable traits is necessary in advancing the effort to deliver precise treatments and achieve better outcomes in patients with UAD.

show abstract

“…In a reassessment of patients included in two previous trials, Leitao Filho et al found that 18-20% of the patients had one or more IgG subclass deficiencies, and that reduced levels of IgG1 and IgG2 were associated with increased risk of acute exacerbations and hospitalizations. 13 Finally, two smaller observational studies found that COPD patients who were on Ig-replacement treatment had fewer acute exacerbations, further suggesting a link between hypogammaglobulinemia and acute exacerbations of COPD. 14,15 The aim of this study was to determine the prevalence of hypogammaglobulinemia in a cohort of stable COPD patients and to relate Ig levels to manifestations of COPD, such as lung function, frequency of exacerbations and self-reported symptoms, and to survival, with the ultimate purpose of facilitating future interventional studies using gammaglobulin replacement therapy in COPD.…”

Section: Introductionmentioning

confidence: 99%

<p>Hypogammaglobulinemia and Risk of Exacerbation and Mortality in Patients with COPD</p>

Holm¹,

Andreassen²,

Christensen³

et al. 2020

COPD

View full text Add to dashboard Cite

Introduction: Chronic obstructive pulmonary disease (COPD) may, in some patients, be characterized by recurring acute exacerbations. Often these exacerbations are associated with airway infections. As immunoglobulins (Ig) are important parts of the immune defence against airway infections, the aim of this study was to relate the levels of circulating immunoglobulins to clinical features in unselected patients with COPD included in a Norwegian multicenter study. Methods: Clinical and biological data, including circulating levels of immunoglobulins, were assessed in 262 prospectively included patients with COPD GOLD stage II-IV at five hospitals in south-eastern Norway. A revisit was done after one year, and survival was assessed after five years. Clinical features and survival of those with immunoglobulin levels below reference values were compared to those with normal levels. Results: In total, 11.5% of all COPD patients and 18.5% of those with GOLD stage IV had IgG concentrations below reference values. These patients were more likely to use inhaled or oral steroids, had lower BMI, and lower FEV1%. Moreover, they had significantly more COPD-related hospital admissions (2.8 vs 0.6), number of prednisolone courses (3.9 vs 1.2), and antibiotic treatments (3.7 vs 1.5) in the preceding year. Importantly, hypogammaglobulinemia was significantly associated with reduced survival in a log-rank analysis. In multivariate regression analysis, we found that the higher risk for acute exacerbations in these patients was independent of other risk factors and was associated with impaired survival. Conclusion: In conclusion, our study suggests that hypogammaglobulinemia may be involved in poor outcome in COPD and may thus be a feasible therapeutic target for interventional studies in COPD.

show abstract

Serum IgG and risk of exacerbations and hospitalizations in chronic obstructive pulmonary disease

Cited by 35 publications

References 9 publications

Cigarette smoking differentially affects immunoglobulin class levels in serum and saliva: An investigation and review

Cigarette smoking differentially affects immunoglobulin class levels in serum and saliva: An investigation and review

Precision medicine in united airways disease: A “treatable traits” approach

<p>Hypogammaglobulinemia and Risk of Exacerbation and Mortality in Patients with COPD</p>

Contact Info

Product

Resources

About