Inhalation therapy represents the standard of care in children, adolescents as well as in young, middle‐aged and geriatric adults with asthma or chronic obstructive pulmonary disease. However, there ...are only few recommendations for the choice of inhalation devices, which consider both, age‐specific limitations in young and geriatric patients. Transition concepts are lacking. In this narrative review, the available device technologies and the evidence for age‐specific problems are discussed.
Pressurized metered‐dose inhalers may be favoured in patients who fulfill all cognitive, coordinative and manual power requirements. Breath‐actuated metered‐dose inhalers, soft‐mist inhalers or the use of add‐on devices such as spacers, face masks and valved holding chambers may be suitable for patients with mild to moderate impairments of these variables. In these cases, available resources of personal assistance by educated family members or caregivers should be used to allow metered‐dose inhaler therapy. Dry powder inhalers may be reserved for patients with a sufficient peak inspiratory flow and good cognitive and manual abilities. Nebulizers may be indicated in persons who are either unwilling or unable to use handheld inhaler devices. After initiation of a specific inhalation therapy, close monitoring is essential to reduce handling mistakes.
An algorithm is developed that considers age and relevant comorbidities to support the decision‐making process for the choice of an inhaler device.
Inhalation therapy is a highly individualized concept of therapy. Age, maturity and comorbidities have to be considered when choosing a specific inhalation device. Standardized algorithms may support this decision process. A close monitoring is essential as it may detect handling mistakes and the need to modify the device concept. A routine reevaluation of the inhalation concept should be implemented with age, maturation and new occurring comorbidities.
•Inhaled antimicrobial prescribing process is multifactorial.•Nebulised tobramycin or colistin are commonly used first-line therapies.•CFTR modulator use may not affect how some physicians prescribe ...inhaled antibiotics.
Prescribers have an increasing range of inhaled antimicrobial formulations to choose from when prescribing both eradication and chronic suppression regimens in cystic fibrosis (CF). This study aimed to investigate the decision-making process behind prescribing of inhaled antimicrobials for Pseudomonas aeruginosa infections.
A questionnaire was developed using Microsoft Forms and then forwarded to 57 Principal Investigators (PIs), at each of the CF centres within the European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN). Data collection occurred between November 2021 and February 2022.
The response rate was 90 % (n = 51/57 PIs), with at least 50 % of CF centers in each of the 17 countries represented in the ECFS-CTN. Physicians used a median of eight factors in their decision-making process with delivery formulations (92.2 %), adherence history (84.3 %), and antibiotic side-effect profile (76.5 %) often selected. Nebulised tobramycin or colistin were frequently selected as the inhaled antimicrobial in first-line eradication (n = 45, 88.2 %) and chronic suppression regimens (n = 42, 82.4 %). Combination regimens were more often chosen in eradication (first-line: n = 35, 68.6 %, second-line: n = 34, 66.7 %) and later chronic suppression regimens (third-line: n = 27, 52.9 %) than monotherapy. For pwCF also prescribed CFTR modulator therapies, most PIs did not alter inhaled antimicrobial regimens (n = 40, 78.4 %), with few pwCF (n = 18, 35.3 %) or PIs (n = 10, 19.6 %) deciding to stop inhaled antimicrobials.
The inhaled antimicrobial prescribing decision-making process is multifactorial. Nebulised tobramycin or colistin are often used in initial eradication and chronic suppression regimens. To date, CFTR modulator therapy has had a limited impact on the prescribing of inhaled antimicrobial regimens.
The strongest genetic risk factor for childhood-onset asthma, the 17q21 locus, is associated with increased viral susceptibility and disease-promoting processes.
To identify biological targets ...underlying the escalated viral susceptibility associated with the clinical phenotype mediated by the 17q21 locus.
Genome-wide transcriptome analysis of nasal brush samples from 261 children (78 healthy, 79 with wheezing at preschool age, 104 asthmatic) within the ALLIANCE (All-Age-Asthma) cohort, with a median age of 10.0 (range, 1.0-20.0) years, was conducted to explore the impact of their 17q21 genotype (SNP
). Concurrently, nasal secretions from the same patients and visits were collected, and high-sensitivity mesoscale technology was employed to measure IFN protein levels.
This study revealed that the 17q21 risk allele induces a genotype- and asthma/wheeze phenotype-dependent enhancement of mucosal
expression as the only relevant 17q21-encoded gene in children with preschool wheeze. Increased
expression correlated with the activation of a type-1 proinflammatory, cell-lytic immune, and natural killer signature, encompassing key genes linked to an IFN type-2-signature (
,
,
,
,
,
). Conversely, there was a reduction in IFN type 1 and type 3 expression signatures at the mRNA and protein levels.
This study demonstrates a novel disease-driving mechanism induced by the 17q21 risk allele. Increased mucosal
expression is associated with a cell-lytic immune response coupled with compromised airway immunocompetence. These findings suggest that
-related airway cell death and perturbations in the mucosal IFN signature account for the increased vulnerability of 17q21 risk allele carriers to respiratory viral infections during early life, opening new options for future biological interventions.The All-Age-Asthma (ALLIANCE) cohort is registered at www.clinicaltrials.gov (pediatric arm, NCT02496468).
RESEARCH QUESTIONPulmonary disease progression in patients with cystic fibrosis (CF) is characterised by inflammation and fibrosis and aggravated by Pseudomonas aeruginosa (Pa). We investigated the ...impact of Pa specifically on: 1) protease/antiprotease balance; 2) inflammation; and 3) the link of both parameters to clinical parameters of CF patients. METHODSTransforming growth factor-β1 (TGF-β1), interleukin (IL)-1β, IL-8, neutrophil elastase (NE) and elastase inhibitor elafin were measured (ELISA assays), and gene expression of the NF-κB pathway was assessed (reverse transcriptase PCR) in the sputum of 60 CF patients with a minimum age of 5 years. Spirometry was assessed according to American Thoracic Society guidelines. RESULTSOur results demonstrated the following: 1) NE was markedly increased in Pa-positive sputum, whereas elafin was significantly decreased; 2) increased IL-1β/IL-8 levels were associated with both Pa infection and reduced forced expiratory volume in 1 s, and sputum TGF-β1 was elevated in Pa-infected CF patients and linked to an impaired lung function; and 3) gene expression of NF-κB signalling components was increased in sputum of Pa-infected patients, and these findings were positively correlated with IL-8. CONCLUSIONOur study links Pa infection to an imbalance of NE and NE inhibitor elafin and increased inflammatory mediators. Moreover, our data demonstrate an association between high TGF-β1 sputum levels and a progress in chronic lung inflammation and pulmonary fibrosis in CF. Controlling the excessive airway inflammation by inhibition of NE and TGF-β1 might be promising therapeutic strategies in future CF therapy and a possible complement to cystic fibrosis transmembrane conductance regulator (CFTR) modulators.
In cystic fibrosis, highly variable glucose tolerance is suspected. However, no study provided within-patient coefficients of variation. The main objective of this short report was to evaluate ...within-patient variability of oral glucose tolerance.
In total, 4,643 standardized oral glucose tolerance tests of 1,128 cystic fibrosis patients (median age at first test: 15.5 11.5; 21.5 years, 48.8% females) were studied. Patients included were clinically stable, non-pregnant, and had at least two oral glucose tolerance tests, with no prior lung transplantation or systemic steroid therapy. Transition frequency from any one test to the subsequent test was analyzed and within-patient coefficients of variation were calculated for fasting and two hour blood glucose values. All statistical analysis was implemented with SAS 9.4.
A diabetic glucose tolerance was confirmed in 41.2% by the subsequent test. A regression to normal glucose tolerance at the subsequent test was observed in 21.7% and to impaired fasting glucose, impaired glucose tolerance or both in 15.2%, 12.0% or 9.9%. The average within-patient coefficient of variation for fasting blood glucose was 11.1% and for two hour blood glucose 25.3%.
In the cystic fibrosis patients studied, a highly variable glucose tolerance was observed. Compared to the general population, variability of two hour blood glucose was 1.5 to 1.8-fold higher.
Severe human bocavirus infection, Germany Körner, Robert Walter; Söderlund-Venermo, Maria; van Koningsbruggen-Rietschel, Silke ...
Emerging infectious diseases,
12/2011, Letnik:
17, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Human bocavirus (HBoV), discovered in 2005, can cause respiratory disease or no symptoms at all. We confirmed HBoV infection in an 8-month-old girl with hypoxia, respiratory distress, wheezing, ...cough, and fever. This case demonstrates that lower respiratory tract infection caused by HBoV can lead to severe and life-threatening disease.
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