Microbiological changes observed over 48 weeks of treatment with inhaled liposomal ciprofloxacin in individuals with non-cystic fibrosis bronchiectasis and chronic Pseudomonas aeruginosa lung infection

ObjectivesNon-cystic fibrosis bronchiectasis (NCFBE) with Pseudomonas aeruginosa has been associated with increased pulmonary exacerbation (PEx) and mortality risk. European Respiratory Society guidelines conditionally recommend inhaled antimicrobials for persons with NCFBE, P aeruginosa and three or more PEx/year. We report microbiological results of two randomized, 48-week placebo-controlled trials of ARD-3150 (inhaled liposomal ciprofloxacin) in individuals with NCFBE with P aeruginosa and PEx history [Lancet Respir Med 2019;7:213–26].MethodsRespiratory secretions from 582 participants receiving up to six 28-day on/off treatment cycles were analysed for sputum P. aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Escherichia coli densities, P. aeruginosa susceptibilities to ciprofloxacin and nine other antimicrobials, and prevalence of other bacterial opportunists. Associations between PEx risk and sputum density, antimicrobial susceptibility and opportunist prevalence changes were studied.ResultsSputum P. aeruginosa density reductions from baseline after ARD-3150 treatments ranged from 1.77 (95% CI 2.13–1.40) versus 0.54 (95% CI 0.89–0.19) log₁₀ CFU/g for placebo (second period) to 2.07 (95% CI 2.45–1.69) versus 0.70 (95% CI 1.11–0.29) log₁₀ CFU/g for placebo (fourth period) with only modest correlation between density reduction magnitude and PEx benefit. ARD-3150 (but not placebo) treatment was associated with increased P. aeruginosa ciprofloxacin MIC but not emergence of other bacterial opportunists across the study; ciprofloxacin MIC₅₀ increased from 0.5 to 1 mg/L, MIC₉₀ increased from 4 to 16 mg/L. Other antimicrobial MIC were mostly unaffected.ConclusionMicrobiological changes over 48 weeks of ARD-3150 treatment appear modest. Ciprofloxacin susceptibility (but not other antimicrobial susceptibility) decreases were observed that did not appear to preclude PEx risk reduction benefit.     

Clinical and laboratory features of seventy-eight UK patients with Good’s syndrome (thymoma and hypogammaglobulinaemia)

Good’s syndrome (thymoma and hypogammaglobulinaemia) is a rare secondary immunodeficiency disease, previously reported in the published literature as mainly individual cases or small case series. We use the national UK-Primary Immune Deficiency (UKPID) registry to identify a large cohort of patients in the UK with this PID to review its clinical course, natural history and prognosis. Clinical information, laboratory data, treatment and outcome were collated and analysed. Seventy-eight patients with a median age of 64 years, 59% of whom were female, were reviewed. Median age of presentation was 54 years. Absolute B cell numbers and serum immunoglobulins were very low in all patients and all received immunoglobulin replacement therapy. All patients had undergone thymectomy and nine (12%) had thymic carcinoma (four locally invasive and five had disseminated disease) requiring adjuvant radiotherapy and/or chemotherapy. CD4 T cells were significantly lower in these patients with malignant thymoma. Seventy-four (95%) presented with infections, 35 (45%) had bronchiectasis, seven (9%) chronic sinusitis, but only eight (10%) had serious invasive fungal or viral infections. Patients with AB-type thymomas were more likely to have bronchiectasis. Twenty (26%) suffered from autoimmune diseases (pure red cell aplasia, hypothyroidism, arthritis, myasthenia gravis, systemic lupus erythematosus, Sjögren’s syndrome). There was no association between thymoma type and autoimmunity. Seven (9%) patients had died. Good’s syndrome is associated with significant morbidity relating to infectious and autoimmune complications. Prospective studies are required to understand why some patients with thymoma develop persistent hypogammaglobulinaemia.     

Bronchiectasis and deteriorating lung function in agammaglobulinaemia despite immunoglobulin replacement therapy

Immunoglobulin replacement therapy enhances survival and reduces infection risk in patients with agammaglobulinaemia. We hypothesized that despite regular immunoglobulin therapy, some patients will experience ongoing respiratory infections and develop progressive bronchiectasis with deteriorating lung function. One hundred and thirty‐nine (70%) of 199 patients aged 1–80 years from nine cities in the United Kingdom with agammaglobulinaemia currently listed on the UK Primary Immune Deficiency (UKPID) registry were recruited into this retrospective case study and their clinical and laboratory features analysed; 94% were male, 78% of whom had Bruton tyrosine kinase (BTK) gene mutations. All patients were on immunoglobulin replacement therapy and 52% had commenced therapy by the time they were 2 years old. Sixty per cent were also taking prophylactic oral antibiotics; 56% of patients had radiological evidence of bronchiectasis, which developed between the ages of 7 and 45 years. Multivariate analysis showed that three factors were associated significantly with bronchiectasis: reaching 18 years old [relative risk (RR) = 14·2, 95% confidence interval (CI) = 2·7–74·6], history of pneumonia (RR = 3·9, 95% CI = 1·1–13·8) and intravenous immunoglobulin (IVIG) rather than subcutaneous immunoglobulin (SCIG) = (RR = 3·5, 95% CI = 1·2–10·1), while starting immunoglobulin replacement after reaching 2 years of age, gender and recent serum IgG concentration were not associated significantly. Independent of age, patients with bronchiectasis had significantly poorer lung function [predicted forced expiratory volume in 1 s 74% (50–91)] than those without this complication [92% (84–101)] (P < 0·001). We conclude that despite immunoglobulin replacement therapy, many patients with agammaglobulinaemia can develop chronic lung disease and progressive impairment of lung function.     

Inhaled ciprofloxacin for chronic airways infections caused by Pseudomonas aeruginosa

Chronic infection of the airways with Pseudomonas aeruginosa represents a therapeutic challenge. Currently existing approaches are particularly based on systemic approaches and this increases the risk of strain resistance selection and is frequently associated with side effects. Therefore, local delivery of antibiotics may reduce these risks and may provide sustained sterilization of the respiratory tract. In fact, this approach was found to be effective with inhaled tobramycin in cystic fibrosis. Inhaled ciprofloxacin (dry powder inhaled formulation or liposomal inhaled formulation) is currently being investigated in chronic infections of the airways in cystic fibrosis, non-cystic fibrosis bronchiectasis and chronic obstructive pulmonary disease, and the initial clinical data are encouraging. This paper presents a perspective on the potential role of inhaled ciprofloxacin in such infections.     

Pulmonary Resection in the Treatment of Life-Threatening Hemoptysis

Purpose: Massive hemoptysis is a life threatening situation with high mortality rates. Surgery is effective, however generally an avoided treatment. We report our experience with patients undergoing lung resection for life-threatening hemoptysis.Methods: Records of all surgically treated patients for hemoptysis between June 2009 and June 2012 were reviewed and analyzed retrospectively.Results: Anatomical resection was performed on 31 (15.3%) patients out of 203 patients referred to our intensive care unit for life-threatening hemoptysis. 25 (80.6%) were male and six (19.4%) were female; with mean age of 46.4 ± 13.7 (21–77). Pneumonectomy was performed in four (12.9%), lobectomy in 24 (77.4%), segmentectomy in two (6.5%) and bilobectomy in one case. Postoperative complications developed in eight (25.8%), and mortality was observed in two (6.5%) patients. Etiology was bronchiectasis in 13 (42.0%), tuberculosis in eight (25.8%), carcinoma in four (12.9%), aspergilloma in four (12.9%), hydatid cyst in one (3.2%) and lung abscess in one (3.2%) of the cases.Conclusions: Although lung resection in the treatment of massive hemoptysis is accompanied with high morbidity and mortality rates, surgery is the only permanent curative modality. Acceptable results can be achived in the company of a multidisciplinary approach, through avoidance of pneumonectomy and urgent surgery.     

Total thoracoscopic combined lingulectomy and pericardial cystectomy

Thoracoscopic anatomic segmentectomy is usually more complex than lobectomy. This video shows a 58-year-old female who suffered from limited bronchiectasis of the lingular segment of the left upper lung and a pericardial cyst on the same side. Both of these benign thoracic diseases can cause pleural adhesions. Repeated chronic inflammation contributes to hypervascularity and lymph node enlargement, making surgery more difficult. We used single-direction thoracoscopic segmentectomy via a three-port approach and successfully removed the lingula and pericardial cyst.     

Recurrent polymyositis triggered by bronchiectasis‐associated infections

Polymyositis is a cell‐mediated autoimmune disease and various systemic infections can trigger it. However, there have been only rare reports of recurrent polymyositis triggered by systemic infections. We report the case of a 69‐year‐old woman with recurrent polymyositis triggered by bronchiectasis‐associated infections. This case indicates that recurrent polymyositis triggered by systemic infections suggests a non‐specific autoimmune antigenic response of polymyositis.