Accuracy of Inhalation Challenge Test for Bird-related Fibrotic Hypersensitivity Pneumonitis: a Case Control Study

Background: The inhalation challenge test is considered to be the “gold standard” for diagnosis of hypersensitivity pneumonitis (HP) and identifying the causative antigen in patients with fibrotic HP. However, the inhalation challenge test is not widely used. This study aimed to examine the value of the inhalation challenge test.Methods: This was a single-center, case control study. The patients with fibrotic HP were diagnosed pathologically by surgical lung biopsy or transbronchial lung cryobiopsy, and were assumed to be bird-related fibrotic HP if they had a history of obvious avian exposure. The patients with a histopathological diagnosis of fibrotic HP, no history of bird exposure and negative anti-bird antibodies were assumed to be non-bird-related fibrotic HP.Results: Based on pathological findings and history of avian exposure, 43 of 86 patients were diagnosed with bird-related fibrotic HP. In 43 patients with bird-related fibrotic HP, 15 (35%) were positive for anti-bird IgG antibody, and 36 (81%) were positive for the inhalation challenge test. Patients with both positive inhalation challenge test and anti-bird IgG antibodies had a 2.7% decline in annual FVC before the inhalation (p = 0.029). In patients with positive inhalation challenge test and the negative anti-bird IgG antibodies, the annual FVC decreased by 5.0% (p = 0.047). No significant FVC decline was observed in patients with negative inhalation challenge test and positive anti-bird IgG antibody, and those with both negative tests.Conclusions: The inhalation challenge test for bird-related fibrotic HP was more sensitive than anti-bird IgG antibodies. Furthermore, the inhalation challenge test was able to find a group of patients with FVC decline.

Comparison of Sodium Lactate Infusion and Carbon Dioxide Inhalation Panic Provocation Tests: A Meta-analysis

Background Sodium lactate (NaL) infusion and carbon dioxide (CO2) inhalation are proven to provoke acute panic attacks (PAs) in patients with panic disorder (PD). A systematic literature search and meta-analysis were performed to compare the effect sizes of these methods. Methods Odds ratios were calculated for each of the original studies and were pooled using the random-effects model. Results Either NaL or CO2 provocations significantly increased the rates of PAs in individuals with PD compared to those in healthy controls. However, the effect size of NaL infusion (OR=25.13, 95% CI=15.48–40.80) was significantly greater than that of CO2 inhalation (OR=10.58, 95%CI=7.88–14.21). Conclusion The evidence for the efficacy of the two panic provocation tests is very strong. Yet, the results support the superiority of NaL infusion over CO2 inhalation challenge as a panic provocation test. Thus, lactate seems a much stronger stimulus than CO2 for the brain suffocation detector.

A case of humidifier lung with a difficult differential diagnosis from COVID-19

ABSTRACT Acute respiratory illnesses that presented with diffuse ground-glass opacities (GGOs) on chest computed tomography (CT) scan suggest the diagnosis of coronavirus disease 2019 (COVID-19). However, many other diseases show similar CT findings, which often offer a difficult differential diagnosis. Here, we report a case of humidifier lung, a rare phenotype of hypersensitivity pneumonitis (HP), which mimicked COVID-19. A 71-year-old man was admitted because of dyspnea and diffuse GGOs found on chest CT scan. Although COVID-19 was initially suspected, his symptoms rapidly improved by the next day. A medical interview revealed that he had started using an ultrasonic humidifier 1 month ago. A high-resolution CT (HRCT) scan showed ill-defined centrilobular nodules and mosaic attenuation, which are typical of HP but atypical of COVID-19. The inhalation challenge test confirmed the diagnosis of humidifier lung. History-taking of humidifier use and a precise HRCT interpretation are helpful to differentiate it from COVID-19.

Neutralizing Concentrations of Anti-Botulinum Toxin Antibodies Positively Correlate with Mouse Neutralization Assay Results in a Guinea Pig Model

Botulinum neurotoxins (BoNT) are some of the most toxic proteins known and can induce respiratory failure requiring long-term intensive care. Treatment of botulism includes the administration of antitoxins. Monoclonal antibodies (mAbs) hold considerable promise as BoNT therapeutics and prophylactics, due to their potency and safety. A three-mAb combination has been developed that specifically neutralizes BoNT serotype A (BoNT/A), and a separate three mAb combination has been developed that specifically neutralizes BoNT serotype B (BoNT/B). A six mAb cocktail, designated G03-52-01, has been developed that combines the anti-BoNT/A and anti-BoNT/B mAbs. The pharmacokinetics and neutralizing antibody concentration (NAC) of G03-52-01 has been determined in guinea pigs, and these parameters were correlated with protection against an inhalation challenge of BoNT/A1 or BoNT/B1. Previously, it was shown that each antibody demonstrated a dose-dependent mAb serum concentration and reached maximum circulating concentrations within 48 h after intramuscular (IM) or intraperitoneal (IP) injection and that a single IM injection of G03-52-01 administered 48 h pre-exposure protected guinea pigs against an inhalation challenge of up to 93 LD50s of BoNT/A1 and 116 LD50s of BoNT/B1. The data presented here advance our understanding of the relationship of the neutralizing NAC to the measured circulating antibody concentration and provide additional support that a single IM or intravenous (IV) administration of G03-52-01 will provide pre-exposure prophylaxis against botulism from an aerosol exposure of BoNT/A and BoNT/B.

Pulmonary Function Testing in Work-Related Asthma: An Overview from Spirometry to Specific Inhalation Challenge

Work-related asthma (WRA) is a very frequent condition in the occupational setting, and refers either to asthma induced (occupational asthma, OA) or worsened (work-exacerbated asthma, WEA) by exposure to allergens (or other sensitizing agents) or to irritant agents at work. Diagnosis of WRA is frequently missed and should take into account clinical features and objective evaluation of lung function. The aim of this overview on pulmonary function testing in the field of WRA is to summarize the different available tests that should be considered in order to accurately diagnose WRA. When WRA is suspected, initial assessment should be carried out with spirometry and bronchodilator responsiveness testing coupled with first-step bronchial provocation testing to assess non-specific bronchial hyper-responsiveness (NSBHR). Further investigations should then refer to specialists with specific functional respiratory tests aiming to consolidate WRA diagnosis and helping to differentiate OA from WEA. Serial peak expiratory flow (PEF) with calculation of the occupation asthma system (OASYS) score as well as serial NSBHR challenge during the working period compared to the off work period are highly informative in the management of WRA. Finally, specific inhalation challenge (SIC) is considered as the reference standard and represents the best way to confirm the specific cause of WRA. Overall, clinicians should be aware that all pulmonary function tests should be standardized in accordance with current guidelines.