The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.

Secondary hypogammaglobulinemia (HGG) from immunosuppression therapy in lung transplant recipients has been associated with increased mortality, morbidity and higher risk of infection. Intravenous immunoglobulin (IVIG) for the treatment of HGG post-lung transplant is not well studied with conflicting evidence regarding efficacy. This single-center, retrospective cohort study analyzed adult lung transplant recipients with HGG receiving ≥1 dose of IVIG 0.3-0.5 g/kg. Resolution of HGG (IgG > 600 mg/dL within 30 days of IVIG) was evaluated for optimal dose and duration of IVIG therapy. Incidence of infection, patient survival, rejection, and chronic lung allograft dysfunction-free survival at 1 year were compared between resolved and persistent HGG. Results demonstrated majority of patients 46/58 (79.3%) achieved HGG resolution. Severe HGG (IgG < 400 mg/dL) was significantly associated with persistent HGG (50.5% vs 15.2%, p = 0.02), with comparable cumulative IVIG dose and duration between both groups (p = 0.96 and p = 0.39, respectively). No other variables correlated with HGG resolution. Overall infection rates were similar between groups (69.6% vs 58.3%, p = 0.50), suggesting HGG resolution did not correlate with incidence of infection. Lastly, use of IVIG for the treatment of HGG appears to be safe with minimal incidence of thrombosis found within each group.

The demographics of lung transplant (LT) recipients show an evolution towards increased minority racial/ethnic representation, thanks to an increased focus on inclusion in LT access, healthcare and outcomes. Herein we assess potential differences in LT allograft health in a predominantly Hispanic/Latino (HL) vs Non-Latino/White (NLW) cohort during surveillance for acute rejection by analyzing the fraction of donor-derived cell-free DNA (dd-cfDNA%), a plasma biomarker of allograft injury. Of 245 LT recipients, median age was younger for HL (n = 108) but no differences for sex or LT type were observed. Of the 1,149 dd-cfDNA% samples, the proportion obtained during the 1st year post-transplant was higher for HL (45.3%) vs NLW (34.3%, p = 0.044), but there were no significant differences during the later periods of 1-5 years (p = 0.341) and 6-10 years (p = 0.096). The median dd-cfDNA% was not different across these time periods. A lower proportion of “High Risk” dd-cfDNA% results (≥1.0%) exhibited graft injury risk in the HL cohort − 33.4% vs 39.6% in the NLW cohort (p = 0.0079), respectively, which was also true for the single lung transplant sub-cohort (p = 7.45 × 10-8). Analysis of intra-patient coefficient of variation for HL vs NLW showed no difference [0.379 (IQR: 0.193-0.540) vs 0.408% (0.254-0.503), p = 0.087]. Our study found no difference in the injury risk by noninvasive dd-cfDNA% assessments, as a metric of organ health, across racial/ethnic groups and further supports clinical value of surveillance in the Hispanic/Latino LT population.