[Severe asthma in adults]. / Ernstig astma bij volwassenen.

The Dutch guideline 'Diagnostics and treatment of severe asthma' provides recommendations on the diagnosis and treatment of patients older than 18 years with severe asthma. A checklist was developed to determine which diagnostic trajectory should be implemented in patients with 'difficult to treat asthma' before the diagnosis of 'severe asthma' can be made. Evidence-based recommendations are made in accordance with the GRADE method, with regard to additional treatment on top of the standard treatment of high dosages of inhaled corticosteroids combined with long-acting beta2 agonists. Furthermore, recommendations are made on the monitoring and follow-up of patients with severe asthma and on the setting up of specialized centres for patients suffering from severe asthma. This guideline is primarily meant for pulmonologists. However, it may also be useful for other disciplines involved in the care for patients with asthma.

Internet-based tapering of oral corticosteroids in severe asthma: a pragmatic randomised controlled trial.

BACKGROUND: In patients with prednisone-dependent asthma the dose of oral corticosteroids should be adjusted to the lowest possible level to reduce long-term adverse effects. However, the optimal strategy for tapering oral corticosteroids is unknown. OBJECTIVE: To investigate whether an internet-based management tool including home monitoring of symptoms, lung function and fraction of exhaled nitric oxide (FE(NO)) facilitates tapering of oral corticosteroids and leads to reduction of corticosteroid consumption without worsening asthma control or asthma-related quality of life. METHODS: In a 6-month pragmatic randomised prospective multicentre study, 95 adults with prednisone-dependent asthma from six pulmonary outpatient clinics were allocated to two tapering strategies: according to conventional treatment (n=43) or guided by a novel internet-based monitoring system (internet strategy) (n=52). Primary outcomes were cumulative sparing of prednisone, asthma control and asthma-related quality of life. Secondary outcomes were forced expiratory volume in 1 s (FEV1), exacerbations, hospitalisations and patient's satisfaction with the tapering strategy. RESULTS: Median cumulative sparing of prednisone was 205 (25-75th percentile -221 to 777) mg in the internet strategy group compared with 0 (-497 to 282) mg in the conventional treatment group (p = 0.02). Changes in prednisone dose (mixed effect regression model) from baseline were -4.79 mg/day and +1.59 mg/day, respectively (p < 0.001). Asthma control, asthma-related quality of life, FEV1, exacerbations, hospitalisations and satisfaction with the strategy were not different between groups. CONCLUSIONS: An internet-based management tool including home monitoring of symptoms, lung function and FE(NO) in severe asthma is superior to conventional treatment in reducing total corticosteroid consumption without compromising asthma control or asthma-related quality of life. Clinical trial registration number Clinical trial registered with http://www.trialregister.nl (Netherlands Trial Register number 1146).

Weekly self-monitoring and treatment adjustment benefit patients with partly controlled and uncontrolled asthma: an analysis of the SMASHING study.

BACKGROUND: Internet-based self-management has shown to improve asthma control and asthma related quality of life, but the improvements were only marginally clinically relevant for the group as a whole. We hypothesized that self-management guided by weekly monitoring of asthma control tailors pharmacological therapy to individual needs and improves asthma control for patients with partly controlled or uncontrolled asthma. METHODS: In a 1-year randomised controlled trial involving 200 adults (18-50 years) with mild to moderate persistent asthma we evaluated the adherence with weekly monitoring and effect on asthma control and pharmacological treatment of a self-management algorithm based on the Asthma Control Questionnaire (ACQ). Participants were assigned either to the Internet group (n = 101) that monitored asthma control weekly with the ACQ on the Internet and adjusted treatment using a self-management algorithm supervised by an asthma nurse specialist or to the usual care group (UC) (n = 99). We analysed 3 subgroups: patients with well controlled (ACQ ACQ 1.5) asthma at baseline. RESULTS: Overall monitoring adherence was 67% (95% CI, 60% to 74%). Improvements in ACQ score after 12 months were -0.14 (p = 0.23), -0.52 (p < 0.001) and -0.82 (p < 0.001) in the Internet group compared to usual care for patients with well, partly and uncontrolled asthma at baseline, respectively. Daily inhaled corticosteroid dose significantly increased in the Internet group compared to usual care in the first 3 months in patients with uncontrolled asthma (+278 microg, p = 0.001), but not in patients with well or partly controlled asthma. After one year there were no differences in daily inhaled corticosteroid use or long-acting beta2-agonists between the Internet group and usual care. CONCLUSIONS: Weekly self-monitoring and subsequent treatment adjustment leads to improved asthma control in patients with partly and uncontrolled asthma at baseline and tailors asthma medication to individual patients' needs.

Exhaled breath profiling enables discrimination of chronic obstructive pulmonary disease and asthma.

RATIONALE: Chronic obstructive pulmonary disease (COPD) and asthma can exhibit overlapping clinical features. Exhaled air contains volatile organic compounds (VOCs) that may qualify as noninvasive biomarkers. VOC profiles can be assessed using integrative analysis by electronic nose, resulting in exhaled molecular fingerprints (breathprints). OBJECTIVES: We hypothesized that breathprints by electronic nose can discriminate patients with COPD and asthma. METHODS: Ninety subjects participated in a cross-sectional study: 30 patients with COPD (age, 61.6 +/- 9.3 years; FEV(1), 1.72 +/- 0.69 L), 20 patients with asthma (age, 35.4 +/- 15.1 years; FEV(1) 3.32 +/- 0.86 L), 20 nonsmoking control subjects (age, 56.7 +/- 9.3 years; FEV(1), 3.44 +/- 0.76 L), and 20 smoking control subjects (age, 56.1 +/- 5.9 years; FEV(1), 3.58 +/- 0.78). After 5 minutes of tidal breathing through an inspiratory VOC filter, an expiratory vital capacity was collected in a Tedlar bag and sampled by electronic nose. Breathprints were analyzed by discriminant analysis on principal component reduction resulting in cross-validated accuracy values (accuracy). Repeatability and reproducibility were assessed by measuring samples in duplicate by two devices. MEASUREMENTS AND MAIN RESULTS: Breathprints from patients with asthma were separated from patients with COPD (accuracy 96%; P < 0.001), from nonsmoking control subjects (accuracy, 95%; P < 0.001), and from smoking control subjects (accuracy, 92.5%; P < 0.001). Exhaled breath profiles of patients with COPD partially overlapped with those of asymptomatic smokers (accuracy, 66%; P = 0.006). Measurements were repeatable and reproducible. CONCLUSIONS: Molecular profiling of exhaled air can distinguish patients with COPD and asthma and control subjects. Our data demonstrate a potential of electronic noses in the differential diagnosis of obstructive airway diseases and in the risk assessment in asymptomatic smokers. Clinical trial registered with www.trialregister.nl (NTR 1282).

Aerosolization of tobramycin (TOBI) with the PARI LC PLUS reusable nebulizer: which compressor to use? Comparison of the CR60 to the PortaNeb compressor.

Aerosol output, aerosol output rate, and aerosol size distribution are influenced by the compressed air flow rate through the nebulizer cup. Testing a nebulizer-compressor with a drug for inhalation in cystic fibrosis (CF) patients is mandatory prior to starting therapy. Tobramycin solution for inhalation (TSI), TOBI, is licensed in Europe with a recommendation for a "suitable" compressor connected to the PARI LC Plus nebulizer. To select a compressor, five devices were tested in a previous in vitro study and this resulted in a subsequent in vivo study. Two compressors [CR60 and PortaNeb (PN)] were compared in an open, randomized, crossover single dose pilot study in 10 CF patients to assess the most suitable device for inhalation of a tobramycin solution (TSI), TOBI, with the PARI LC Plus nebulizer. Lung function (FEV1 and FVC), pharmacokinetics [PK; safety (Cmax, Ctrough)], lung deposition (indirect method AUC0-6), nebulization time, and patients' experiences (questionnaire) were determined and compared. It was found that values of Cmax and AUC0-6 were higher with the CR60 than with the PortaNeb: 0.70 versus 0.54 mg/L, p = 0.005, and 2.54 versus 2.01 h.mg/L, p = 0.017, respectively. Tmax after use of the CR60 appeared earlier (0.64 vs. 0.85 h, p = 0.005). Transient airway narrowing was measured in three patients (2 x PN;1 x CR60) versus subjective chest tightness in seven patients (CR60 > PN). A shorter nebulization time for CR60 of 13.2 min compared to PN 16.1 min (p = 0.022) was observed, which was the main reason why patients preferred the CR60 (n = 7). No toxic serum levels were reached after inhalation of TSI. The CR60 compressor may seem advantageous based on a higher lung deposition and a shorter nebulization time, but a study in a large CF population to provide information on a possible higher risk of toxicity of TSI is called for.

Metastases in supraclavicular lymph nodes in lung cancer: assessment with palpation, US, and CT.

PURPOSE: To compare ultrasonography (US), computed tomography (CT), and palpation for diagnosing supraclavicular lung cancer metastases and to assess the effect of proved metastases on TNM stage and diagnostic work-up. MATERIALS AND METHODS: One hundred seventeen consecutive patients (91 men and 26 women; mean age, 64.0 years) underwent palpation, US, and CT of supraclavicular regions and chest and upper abdominal CT. Fine-needle aspiration cytologic (FNAC) analysis was performed in patients with nodes with a short-axis diameter of 5 mm or greater; cytologic diagnosis was used as the standard of reference. Sensitivities of palpation, US, and CT were compared with McNemar testing. Relationship between size and palpability of nodes with metastasis was evaluated with logistic regression. RESULTS: Supraclavicular metastases were diagnosed cytologically in 30 (26%) of 117 patients: eight (31%) of 26 patients with small cell lung cancer (SCLC) and 22 (24%) of 91 patients with non-small cell lung cancer (NSCLC). Sensitivities of US (1.00; 30 of 30 patients) and CT (0.83; 25 of 30 patients) for detection of metastases were significantly higher (P <.001 and P =.001, respectively) than that of palpation (0.33; 10 of 30 patients). Palpable nodes with metastasis (mean diameter, 25.2 mm) were significantly larger than nonpalpable nodes with metastasis (mean diameter, 13.7 mm) (P =.002). To have a 50% chance of being palpable, nodes with metastasis had to have a diameter of at least 22.3 mm. TNM stage was changed in three of 91 patients with NSCLC, and further invasive diagnostic procedures were prevented in 11 of such patients because it was proved that nonpalpable nodes had metastases. CONCLUSION: Supraclavicular lung cancer metastases were cytologically proved in 26% of patients. Nodes with metastasis were only palpable when markedly enlarged. US tripled the sensitivity of palpation for detection of metastases. Results of US and US-guided FNAC analysis can change the work-up in patients with lung cancer.