Appropriate lung management in patients with primary antibody deficiencies

ABSTRACT

Introduction: Human primary immunodeficiency diseases (PIDs) include a broad spectrum of more than 350 disorders, involving different branches of the immune system and classified as ‘rare diseases.’ Predominantly antibody deficiencies (PADs) represent more than half of the PIDs diagnosed in Europe and are often diagnosed in the adulthood.

Areas covered: Although PAD could first present with autoimmune or neoplastic features, respiratory infections are frequent and respiratory disease represents a relevant cause of morbidity and mortality. Pulmonary complications may be classified as infection-related (acute and chronic), immune-mediated, and neoplastic.

Expert opinion: At present, no consensus guidelines are available on how to monitor and manage lung complications in PAD patients. In this review, we will discuss the available diagnostic, prognostic and therapeutic instruments and we will suggest an appropriate and evidence-based approach to lung diseases in primary antibody deficiencies. We will also highlight the possible role of promising new tools and strategies in the management of pulmonary complications. However, future studies are needed to reduce of diagnostic delay of PAD and to better understand lung diseases mechanisms, with the final aim to ameliorate therapeutic options that will have a strong impact on Quality of Life and long-term prognosis of PAD patients.

KEYWORDS:

• Primary antibody deficiencies
• GLILD
• CVID
• bronchiectasis
• lung MRI

Article highlights

• Internationally recognized evidence-based guidelines need to be designed, in order to standardize the approach to diagnosis, monitoring, and treatment of lung diseases in PAD. This will go through technical improvements and new acquisitions in terms of pathogenic mechanisms and will reduce the diagnostic delay of lung complications, improving patients’ QoL and survival.

• IgG replacement therapy enhances survival and reduces severe and invasive infections. However, patients might still develop chronic infection-related lung disease (CLD). Adjunct therapies as Azithromycin prophylaxis, pulmonary rehabilitation, and new IgA and IgM enriched Ig preparations that will soon be available need to be included in standardized guidelines, in order to prevent the progression of CLD.

• HRCT scan still represents the gold standard for lung imaging in PADs. Recent evidence supports the possible role of lung magnetic resonance imaging (MRI) in diagnosing and monitoring lung disease in PAD patients. Without exposure to ionizing radiation, recently developed chest MRI techniques might offer both structural and functional information in a single examination. MRI is thus destined to become a routinely used lung imaging approach for PAD patients.

• GLILD, whose diagnosis is currently based on a multi-step process culminating in an invasive open-lung or VATS biopsy, still represents a great challenge. In the next future, the diagnostic process will hopefully move to a more clinical-radiologic-plus-MDT-discussion-based approach, with an increasing importance of BAL. Cryo-biopsy will likely become the first-line approach when a lung tissue biopsy is needed.

• In terms of treatment, we are looking for interesting correlations between GLILD behavior and possible predisposing factors, underlying genetic defects, concomitant conditions, peripheral blood or BALF lymphocytes distribution, histochemical characterization of tissue samples. These correlations will emerge from ongoing observational studies and from case series, allowing clinicians to consider more tailored treatment strategies either on the basis of patients’ classification in subgroups, or starting from the immunologic mechanisms highlighted in each single patient.

• Starting from a better understanding of mechanisms and correlations, relatively large multicenter-controlled trial with existing drugs will be designed, hopefully leading to PAD-specific evidence-based treatment guidelines for ILDs.

Acknowledgments

Thanks to Nicholas Landini, MD, Department of Radiology, Ca’ Foncello Hospital, Treviso, Italy, for his contribution to the selection of the radiologic images.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.