Background: The frequency of clinical isolation of nontuberculous mycobacteria (NTM) in the Netherlands is increasing, but its clinical relevance is often uncertain. Objective: To assess the frequency and clinical relevance of isolation of NTM in four associated hospitals in a single region in the Netherlands. Methods: Medical files of all patients from whom NTM were isolated between January 1999 and January 2005 were reviewed retrospectively. Diagnostic criteria for nontuberculous mycobacterial disease published by the American Thoracic Society (ATS) were used to determine clinical relevance. Results: 232 patients were found, from whom NTM were isolated from the respiratory tract in 91% of cases. Patients were mostly white men, with an average age of 60 years and pre-existing pulmonary disease. Fifty-three of 212 patients (25%) with pulmonary isolates met the ATS diagnostic criteria for pulmonary NTM disease; this percentage differed by species. Most patients were treated with rifampicin, ethambutol and clarithromycin. Treatment outcome for pulmonary NTM disease was suboptimal but differed by species: overall, improvement was seen in 67% of treated patients, but in only 50% of those with pulmonary M avium disease. Lymphadenitis was the most common extrapulmonary disease type. Conclusions: Twenty-five per cent of all patients with pulmonary NTM isolates met the ATS criteria. Clinical relevance differs by species. NTM isolation increases over time. Species distribution differs from that of neighbouring countries and the M avium complex isolates have traits different from those reported in the USA. Adherence to diagnostic and treatment guidelines can be improved.The clinical isolation of non-tuberculous mycobacteria (NTM) increases in many countries where the incidence of tuberculosis is decreasing, with marked geographical differences in the species encountered.

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.

In the Netherlands, isolation of Mycobacterium xenopi is infrequent, and its clinical relevance is often uncertain. To determine clinical relevance and determinants, we retrospectively reviewed medical fi les of all patients in the Netherlands in whom M. xenopi was isolated from January 1999 through March 2005 by using diagnostic criteria for nontuberculous mycobacterial infection published by the American Thoracic Society. We found 49 patients, mostly white men, with an average age of 60 years and pre-existing pulmonary disease; of these patients, 25 (51%) met the diagnostic criteria. Mycobacterial genotype, based on 16S rRNA gene sequencing, was associated with true infection. Most infections were pulmonary, but pleural and spinal infections (spinal in HIV-infected patients) were also noted. Treatment regimens varied in content and duration; some patients were overtreated and some were undertreated. M ycobacterium xenopi was fi rst described by Schwabacher in 1959; it was isolated from skin lesions in a clawed frog and named after the offi cial species designation of the frog, Xenopus laevis (1). Thereafter, these slowgrowing mycobacteria have been recovered from heated water systems in many countries and more recently from natural waters in Finland (2). Transmission to humans is believed to originate from the environment, through aerosol inhalation or ingestion. Human-to-human transmission and transmission from animal reservoirs remain controversial because these routes have not been proven by molecular typing (3,4).Pulmonary M. xenopi infections are most common, but extrapulmonary and disseminated infections have also been recorded (5,6). A predisposing factor is impaired immunity, either local (e.g., pre-existing pulmonary disease) or systemic (e.g., hematologic malignancy, immunosuppressive medication, or HIV/AIDS) (5,7).Its survival in fl owing water systems and resistance to common disinfectants enables M. xenopi to contaminate laboratory samples and medical devices such as bronchoscopes, thus causing healthcare-acquired (pseudo) infections and laboratory cross-contaminations (3,6,8,9). Differentiating true infection from pseudoinfection is of paramount importance because treatment of M. xenopi infections is time-consuming and often complicated. The British Thoracic Society (BTS) trial in 2001 established that treatment for pulmonary infections should consist of a 2-year course of rifampin and ethambutol; regimens including macrolides or fl uoroquinolones are still being investigated (10). The American Thoracic Society (ATS) established general criteria for the diagnosis and treatment of nontuberculous mycobacterial, not specifi cally M. xenopi, infections. The treatment guidelines are similar to those by the BTS, although the ATS guidelines advocate macrolidecontaining regimens (5).To assess frequency and clinical relevance of M. xenopi isolation and its determinants in the Netherlands, we performed a retrospective case study. We used the ATS diagnostic criteria available during the study period to diff...

Currently available European Alpine Altitude Climate Treatment (AACT) programs combine the physical characteristics of altitude with the avoidance of environmental triggers in the alpine climate and a personalized multidisciplinary pulmonary rehabilitation approach. The reduced barometric pressure, oxygen pressure, and air density, the relatively low temperature and humidity, and the increased UV radiation at moderate altitude induce several physiological and immunological adaptation responses. The environmental characteristics of the alpine climate include reduced aeroallergens such as house dust mites (HDM), pollen, fungi, and less air pollution. These combined factors seem to have immunomodulatory effects controlling pathogenic inflammatory responses and favoring less neuro‐immune stress in patients with different asthma phenotypes. The extensive multidisciplinary treatment program may further contribute to the observed clinical improvement by AACT in asthma control and quality of life, fewer exacerbations and hospitalizations, reduced need for oral corticosteroids (OCS), improved lung function, decreased airway hyperresponsiveness (AHR), improved exercise tolerance, and improved sinonasal outcomes. Based on observational studies and expert opinion, AACT represents a valuable therapy for those patients irrespective of their asthma phenotype, who cannot achieve optimal control of their complex condition despite all the advances in medical science and treatment according to guidelines, and therefore run the risk of falling into a downward spiral of loss of physical and mental health. In the light of the observed rapid decrease in inflammation and immunomodulatory effects, AACT can be considered as a natural treatment that targets biological pathways.

Allergic diseases like asthma, allergic rhinitis, food allergy, hymenoptera allergy, or atopic dermatitis are highly prevalent in women of childbearing age and may affect up to 30% of this age group. This review focuses on the management of allergic diseases during pregnancy. Furthermore, we discuss the challenges of counseling women with allergic diseases in the reproductive age, including considerations relevant to the ongoing SARS-CoV-2 pandemic. To create the optimal milieu for the unborn child, a multitude of immunological changes occur during pregnancy which may favor type 2 responses and aggravate disease phenotypes. In co-occurrence with suboptimal preconception disease control, this elevated Th2 responses may aggravate allergic disease manifestations during pregnancy and pose a risk for mother and child. Due to limitations in conducting clinical trials in pregnant women, safety data on anti-allergic drugs during pregnancy are limited. The lack of information and concerns among pregnant patients demands counseling on the benefits of anti-allergic drugs and the potential and known risks. This includes information on the risk for mother and child of disease aggravation in the absence of treatment. By doing so, informed decisions and shared decision-making can take place.