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Biomedical subjects

H A Tiddens

Publications and source records attributed to H A Tiddens.

At least 19 recordsLinked to original sources
PubMed2006

Effect of dry powder inhaler resistance on the inspiratory flow rates and volumes of cystic fibrosis patients of six years and older.

Several inhaled drugs for use by cystic fibrosis (CF) patients are formulated for nebulizer use only. This therapy is time consuming and includes the risk of contamination of the nebulizers. Dry powder inhalers (DPI) can be an attractive alternative for CF drugs. Inhaled flow rate and volume, and the device resistance are important determinants for optimal dispersion of drug from a DPI. It is important to understand how these variables interact in the CF population in order to properly design a new DPI formulation targeted for these patients. The objective of this study was to assess the inspiratory variables of a representative population of CF subjects 6 years and older with varying degrees of lung disease while inhaling through resistances that simulate DPI devices. Ninety-six stable CF patients were enrolled, ages 6-54 years, FEV(1) 19-126% predicted. Subjects inhaled forcefully through four different resistances (0.019, 0.024, 0.038, and 0.048 kP(0.5)/LPM, respectively), while inspiratory time (IT(DPI)), peak inspiratory flow (PIF(DPI)), and volumes (V(DPI)) were measured. For any resistance, inspired V(DPI) increased with the older age groups; PIF(DPI) was similar between adults and adolescents but lower in the children. Subjects with lower FEV(1) had lower V(DPI) and PIF(DPI). As resistance increased, PIF(DPI) decreased, IT(DPI) increased, with no significant change in V(DPI). At the lowest resistance mean PIF(DPI) was 105 LPM (range 45-163) for all patients; 112 LPM (range 75-163) in adults; and 89 LPM (45-126) in children. Mean inspired V(DPI) was 1.75 L for all patients; 2.2 L (0.8-3.7) in adults; and 1.2 L (0.5-1.8) in children. At the lowest resistance a minimal flow rate of 30, 45, and 60 LPM was attained in 100%, 99%, and 96% of all patients. Volumes of 1.0, 1.5, and 2.0 L were attained by 85%, 57%, and 30% of the patients. At the highest resistance mean PIF(DPI) was 52 LPM (range 26-70) for all patients; 55 LPM (40-70) in adults; and 47 LPM (26-62) in children. Mean inspired V(DPI) was 1.5 L in all patients; 1.9 L (0.9-3.5) in adults and 1.1 L (0.5-2.3) in children. At the highest resistance, a minimal flow rate of 30, 45, and 60 LPM was attained in 99%, 80%, and 22% of all patients. Volumes of 1, 1.5, and 2 L were attained in 84%, 45%, and 23% of the patients. We defined ranges for inspiratory variables in a diverse CF population for a range of device resistances that bracket those of current DPIs. The recorded inspiratory patterns can be used on the bench to design and test new dry powder formulations and devices to target the largest proportion of the CF population.

Adolescent↗
PubMed2006

Computed tomographic estimation of lung dimensions throughout the growth period.

The aim of the current study was to use computed tomography (CT) to estimate airway wall and lumen, and arterial and parenchyma dimensions in children throughout the growth period, and to provide normative data to study alterations caused by pulmonary disease. Clinical CT scans reported as normal that were performed in children for nonpulmonary and noncardiac reasons were analysed for lung weight, gas volume, lung expansion, lung surface/volume ratio, airway wall area, airway lumen area, airway lumen perimeter, arterial area and airway surface length/area ratio. The age range of the 50 subjects was 0-17.2 yrs. The data showed only little increase in lung expansion throughout childhood (n = 32). There was substantial variability in lung expansion between subjects. Airway wall and lumen and arterial area were exponentially associated with subjects' height (n = 50). Airway surface length/area ratio was linearly associated to alveolar surface/volume ratio. The data from the current study provide normative computed tomography estimates of airway wall and lumen, and arterial and parenchyma dimensions throughout the growth period that may be useful for the study of alterations in disease.

Adolescent↗
PubMed2003

Estimation of lung growth using computed tomography.

Anatomical studies suggest that normal lungs grow by rapid alveolar addition until about 2 yrs of age followed by a gradual increase in alveolar dimensions. The aim of this study was to examine the hypothesis that normal lung growth can be monitored by computed tomography (CT). Therefore, the gas volume per gram of lung tissue was estimated from measurements of lung density obtained from CT scans performed on children throughout the growth period. CT scans were performed on 17 males and 18 females, ranging in age from 15 days-17.6 yrs. CT-measured lung weight was correlated with predicted post mortem values and CT measured gas volume with predicted values of functional residual capacity. The median value for lung expansion was 1.86 mL x g(-1) at 15 days, decreased to 0.79 mL x g(-1) by 2 yrs and then increased steadily to 5.07 mL x g(-1) at 17 yrs. Computed tomography scans can be used to estimate lung weight, gas volume and expansion of normal lungs during the growth period. The increase in the lung expansion after the age of 2 yrs suggests progressive alveolar expansion with increasing lung volume.

Adolescent↗
PubMed2001

A two-year randomized, placebo-controlled trial of dornase alfa in young patients with cystic fibrosis with mild lung function abnormalities.

OBJECTIVE: Our objective was to determine whether long-term treatment of young patients with cystic fibrosis (CF) with dornase alfa maintains lung function and reduces respiratory tract exacerbations. STUDY DESIGN: This was a 96-week, randomized, double-blind, placebo-controlled trial involving 49 CF centers. Inclusion criteria were age 6 to 10 years and forced vital capacity > or = 85% predicted. Patients were excluded for hospitalization for complications of CF within 2 months and use of dornase alfa within 6 months. Patients were treated with dornase alfa 2.5 mg or placebo once daily with a jet nebulizer and a compressor. RESULTS: Patients were randomized, 239 to dornase alfa and 235 to placebo. At baseline the mean age was 8.4 years, the mean forced expiratory volume in 1 second 95% predicted, the mean forced expiratory flow, midexpiratory phase 85% predicted, and the mean forced vital capacity 102% predicted. At 96 weeks the treatment benefit for dornase alfa compared with placebo in percent predicted (mean +/- SE) was 3.2 +/- 1.2 for forced expiratory volume in 1 second (P =.006), 7.9 +/- 2.3 for forced expiratory flow between 25% and 75% of vital capacity (P =.0008), and 0.7 +/- 1.0 for forced vital capacity (P =.51). The risk of respiratory tract exacerbation was reduced by 34% in patients who received dornase alfa (relative risk 0.66, P =.048). There was no statistically significant difference between the groups in changes in weight-for-age percentile. Adverse event profiles for the treatment groups were similar. CONCLUSIONS: Treatment of young patients with CF with dornase alfa maintains lung function and reduces the risk of exacerbations over a 96-week period.

Age Factors↗
PubMed2001

The Sophia Anatomical Infant Nose-Throat (Saint) model: a valuable tool to study aerosol deposition in infants.

Relatively little is known about the variables that influence lung deposition of inhaled aerosols in children. A model of the upper airways of an infant could be a useful tool to study these variables in vitro. The objective of this study was to construct an anatomically correct model of the upper airways of a young child. A routine three-dimensional (3D) CT scan of the skull and neck of a child was selected that included the airway from the nasal cavity down to the subglottic region. The CT scan was edited to obtain an anatomically correct distinction between air and mucosa. Next, a model was constructed with a stereolithographic technique using a UV-sensitive resin. To validate the model, a 3D CT scan of the model was made and compared to the anatomy of the original image. To study aerosol deposition, the model was connected to a breathing simulator. Medical aerosols were delivered to the model by MDI/spacer during stimulated breathing. An upper airway model was made of a 9-month-old child that needed reconstructive surgery for a skull deformity and with normal anatomy of the upper airways. The nasal airway of the model was open for air passage and the oral airway was closed. The CT scan of the model matched the original in vivo CT scan closely. Aerosol deposition measurements showed that dose passing the model, or lung dose, was comparable with in vivo lung deposition data. We have constructed an anatomically correct model of the upper airways of a child, using a stereolithographic method for in vitro studies of aerosol deposition in young children. This model will be used to obtain insight in aerosol treatment that cannot be obtained in vivo.

Aerosols↗
PubMed2000

Aerosol therapy in cystic fibrosis: a survey of 54 CF centers.

Aerosol therapy has become increasingly important in the treatment of lung disease of patients with cystic fibrosis (CF). Still, many questions concerning this therapy remain unanswered. It is unclear at what age aerosol therapy should be started; which aerosolized drugs are essential in the treatment of CF lung disease; which delivery system(s) should be used; and how aerosol therapy should be timed in relation to physiotherapy. We hypothesized that large differences in aerosol treatment practices between CF centers would be present. To investigate this, we performed an observational survey to evaluate different aspects of aerosol therapy. A questionnaire was sent to 102 CF centers in 28 different countries. A completed questionnaire was returned by 54 out of 94 centers (57%). In these 54 centers, 7,324 CF patients were treated. Substantial differences were found in aerosol therapy between centers. Patients below age 1 year were not treated with any form of aerosol therapy in 10% of the centers, while 37.5% of the centers treated all of these patients. The timing of nebulization and physiotherapy varied substantially for many important and expensive drugs. We conclude that many aspects of aerosol therapy in cystic fibrosis need to be executed in a more rational and evidence-based manner than is currently the case.

Administration, Inhalation↗
PubMed2000

Cartilaginous airway wall dimensions and airway resistance in cystic fibrosis lungs.

It is not clear how airway pathology relates to the severity of airflow obstruction and increased bronchial responsiveness in cystic fibrosis (CF) patients. The aim of this study was to measure the airway dimensions of CF patients and to estimate the importance of these dimensions to airway resistance using a computational model. Airway dimensions were measured in lungs obtained from CF patients who had undergone lung transplantation (n=12), lobectomy (n=1), or autopsy (n=4). These dimensions were compared to those of airways from lobectomy specimens from 72 patients with various degrees of chronic obstructive pulmonary disease (COPD). The airway dimensions of the CF and COPD patients were introduced into a computational model to study their effect on airway resistance. The inner wall and smooth muscle areas of peripheral CF airways were increased 3.3- and 4.3-fold respectively compared to those of COPD airways. The epithelium was 53% greater in height in peripheral CF airways. The sensitivity and maximal plateau resistance of the computed dose/response curves were substantially increased in the CF patients compared to COPD patients. The changes in airway dimensions of cystic fibrosis patients probably contribute to the severe airflow obstruction, and to increased bronchial responsiveness, in these patients.

Adolescent↗
PubMed2000

Aerosol delivery from spacers in wheezy infants: a daily life study.

The aims of this study were to assess and compare dose delivery and dose variability of pressurized metered dose inhalers (pMDI)/spacers in wheezy infants in daily life and to investigate factors influencing aerosol delivery. In an open randomized crossover study in 25 wheezy infants aged 5-26 months, a metal spacer (Nebuchamber), a detergent coated (DC) and a non-detergent coated (nonDC) plastic spacer (Babyhaler) were tested at home for 7 days each. Budesonide (200 microg b.i.d) was administered via a Nebuchamber or fluticasone (125 microg b.i.d) via a Babyhaler. Aerosol was trapped in filters, positioned between the spacer and face mask. Cooperation was scored on diary cards. Electrostatic charge (ESC) of the spacers was measured. Evaluations of the administration technique were made from video recordings. Median (range) dose delivery of the filters expressed as per cent (%) of nominal dose, was 34% (3-59), 23% (1-49), and 41% (12-55) for the Nebuchamber, nonDC-Babyhaler, and DC-Babyhaler respectively. Considerable dose variability was found, median (range) within-subject dose variability, expressed as coefficient of variation, for the Nebuchamber (49% (15-249)) was significantly higher when compared with both nonDC- (36% (12-325)) and DC-Babyhalers (27% (10-122)), for which dose variabilities were similar. Detergent coating was effective to reduce electrostatic charge, and to increase dose delivery, but had no effect on dose variability. Bad cooperation was an important cause for high dose variability for all spacers (r=0.5-0.6, p<0.02). Many mistakes were made during the administration procedure.

Aerosols↗
PubMed1999

Variability of aerosol delivery via spacer devices in young asthmatic children in daily life.

Pressurized metered dose inhalers (pMDI) are widely used together with spacers for the treatment of asthma in children. However, the variability of daily medication dose for pMDI/spacer combinations is not known. Electrostatic charge is a potential source of dose variability. Metal spacers have no static charge. This study assessed and compared within-subject variability of aerosol delivery of metal and plastic spacers. This was a randomized, crossover study in children with stable asthma aged 1-4 (group I, n=17) and 5-8 (group II, n=16) yrs. In both groups the amount of drug delivered to the mouth by a metal spacer (Nebuchamber) and one of two plastic (polycarbonate) spacers, i.e. Babyhaler in group I and Volumatic in group II was measured. The metal and plastic spacers were tested at home in a randomized order for 7 days each, using budesonide (200 microg b.i.d.). Aerosol was collected on a filter positioned between spacer and facemask or mouth. Budesonide on the filter was assessed by high performance liquid chromatography. The mean filter dose for each child (mean+/-SD) during the 7 days was expressed as a percentage of the nominal dose. Within-subject variability was expressed as coefficient of variation (CV). Mean filter dose in group I was 41.7+/-10.1% for Nebuchamber and 26.0+/-4.0% for Babyhaler (p<0.001). Mean filter dose in group II was 50.2+/-9.2% for Nebuchamber and 19.4+/-7.2% for Volumatic (p<0.001). Mean CV in group I was 34% for Nebuchamber and 37% for Babyhaler (p=0.44). Mean CV in group II was 23% for Nebuchamber and 34% for Volumatic (p=0.003). There was substantial within-subject dose variability in aerosol delivery in children using a pMDI/spacer at home. This variability was lower for the metal than for the plastic spacer in children 5-8 yrs of age. The dose delivered to the mouth was about two-fold higher for the metal than the plastic spacer independent of age.

Aerosols↗
PubMed1999

Compliance, hysteresis, and collapsibility of human small airways.

We tested the hypothesis that airway wall dimensions are important determinants for the mechanical properties of airways. Lung tissue was obtained from 31 smokers with different degrees of chronic obstructive pulmonary disease (COPD) who were operated on for a solitary lung lesion. Segments of small airways (n = 35) were mounted on cannulas in an organ bath and inflated and deflated cyclically between +15 and -15 cm H(2)O. For each airway this was done at baseline, after methacholine, and after isoprenaline. Specific compliance (sCdyn), specific hysteresis (seta), and pressure at which the airways collapsed (Pcol) were calculated from each recording. Airway wall dimensions were measured morphometrically. Lung function parameters of airflow obstruction were correlated to sCdyn, seta, and Pcol. At baseline, after methacholine, and after isoprenaline sCdyn was 0.059, 0.052, and 0. 085 cm H(2)O(-)(1), seta was 13.5, 12.9, and 7.1%, and Pcol was -3.4, -3.5, and -1.9 cm H(2)O, respectively. Differences between sCdyn, seta, and Pcol after methacholine and after isoprenaline were highly significant (p < 0.001). Of all dimensions studied, smooth muscle area, but not total wall area, was the most important determinant for sCdyn and for seta after methacholine. Specific hysteresis at baseline correlated to residual volume as a fraction of total lung capacity (RV/TLC) (r = 0.5, p = 0.05) and, in the presence of methacholine, to FEV(1)/FVC (r = -0.68, p = 0.02) and RV/TLC (r = 0. 5, p = 0.05). We conclude that, in this study, smooth muscle area and smooth muscle tone, but not total wall area, are determinants for compliance, hysteresis, and collapsibility of isolated airways obtained from smokers.

Adult↗
PubMed1998

The micro-plethysmograph: a new device to measure small volume displacements by isolated human airway segments.

For the study of airway responsiveness in vitro, airway segments have important advances over strip or spiral preparations. The method to study isobaric contraction of segments is not well established. The aim of this work was to develop a model to assess the smooth muscle responses in isolated airway segments under isobaric conditions. We developed a microplethysmograph with a volume measurement range of 10 to 700 microL, a resolution of 0.02-0.4 microL, and a drift of 2.6-0.7% of measurement range min(-1) for its most and least sensitive setting, respectively. The plethysmograph is able to compensate for the pressure changes induced by the volume changes, enabling for true isobaric measurements. We show examples of the isobaric contraction and relaxation of isolated human airway segments after stimulation of an airway segment by methacholine, isoprenaline, or electrical field stimulation. Apart from studying airway responses, the micro-plethysmograph is potentially useful to study the contractile properties of watertight and hollow structures like blood vessels, gut, and ureter. In addition, this device can be used to measure leak or diffusion at any transmural pressure.

Air Pressure↗
PubMed1996

[Problems in the use, cleaning and maintenance of nebulization equipment in the home situation].

OBJECTIVE: To determine whether jet nebulizers used at home for the treatment of children with asthma are used optimally. DESIGN: Descriptive. SETTING: Outpatient clinic for child pulmonary diseases of the Academic Hospital/Sophia Children's Hospital Rotterdam and outpatient clinic for child diseases of the Baronie Hospital Breda, the Netherlands. METHOD: Thirty-nine children aged 0-13 years and their parents were interviewed at home, and medication cup, saline and aerosol were cultured for bacterial analysis. The pressures of the compressor and nebulizer were measured with a manometer, and the particle size of the aerosol of 10 jet nebulizers was measured by laser technique. RESULTS: The suppliers of the nebulizer did not provide clear instructions on user-related aspects and technical maintenance of the jet nebulizer. Many patients used damaged and poorly functioning, contaminated jet nebulizers. Contamination by potentially pathogenic micro-organisms was present in 50% of the saline, medication cups and aerosols (Klebsiella, Enterobacter, Pseudomonas, Serratia, Escherichia coli). The operating pressure of compressor and nebulizer was below the requirements in more than 50% of the jet nebulizers. In addition, we found that the aerodynamic mass median diameter increased considerably as the nebulizer became older. In 6/10 nebulizers the particle size was below 5 microns. CONCLUSION: A periodical checkup of user-related aspects and technical quality of jet nebulizers is necessary. The quality of the instruction to users about the procedure for cleaning and maintenance of the jet nebulizer should be improved.

Asthma↗
PubMed1996

Pulmonary diffusing capacity at reduced alveolar volumes in children.

The diffusing capacity, when normalized per liter of alveolar volume (DL,CO/VA) decreases in normal adults, whereas their total diffusing capacity (DL,CO) increases as alveolar volume (VA) increases. We studied these relationships in a group of normal children below 20 years of age. Diffusion variables were determined using the single breath technique. The effects of sex, age, and height on these relationships were estimated. DL,CO increased and DL,CO/VA decreased as alveolar volume increased. DL,CO and DL,CO/VA reference values at total lung capacity (TLC) appeared to be comparable to reference values at TLC in the literature. Reference values of DL,CO and DL,CO/VA derived from measurements at various alveolar volumes also predict similar values at TLC. The advantage of our reference equations is their applicability to patients with restrictive lung disease. Actual DL,CO/VA can be compared with reference DL,CO/VA at actual (restrictive) TLC instead of reference DL,CO/VA at reference TLC. This comparison extends the evaluation of a diffusion disorder.

Adolescent↗
PubMed1996

Physiological and morphological determinants of maximal expiratory flow in chronic obstructive lung disease.

Maximal expiratory flow in chronic obstructive pulmonary disease (COPD) could be reduced by three different mechanisms; loss of lung elastic recoil, decreased airway conductance upstream of flow-limiting segments; and increased collapsibility of airways. We hypothesized that decreased upstream conductance would be related to inflammation and thickening of the airway walls, increased collapsibility would be related to decreased airway cartilage volume, and decreased collapsibility to inflammation and thickening of the airway walls. Lung tissue was obtained from 72 patients with different degrees of COPD, who were operated upon for a solitary peripheral lung lesion. Maximal flow-static recoil (MFSR) plots to estimate upstream resistance and airway collapsibility were derived in 59 patients from preoperatively measured maximal expiratory flow-volume and pressure-volume curves. In 341 transversely cut airway sections, airway size, airway wall dimensions and inflammatory changes were measured. Airflow obstruction correlated with lung elastic recoil and the MFSR estimate of airway conductance but not to airway collapsibility or to the amount of airway cartilage. The upstream conductance decreased as the inner wall became thicker. Airway collapsibility did not correlate with the amount of airway cartilage, inflammation, or airway wall thickness. We conclude that the maximal flow-static recoil model does not adequately reflect the collapsibility of the flow-limiting segment.

Adult↗
PubMed1995

Staphylococcal pneumonia in childhood: will early surgical intervention lower mortality?

Staphylococcus aureus pneumonia (SAP) continues to be a serious bacterial infection which is associated with a high incidence of complications. We retrospectively reviewed the case records of 36 infants and children admitted with SAP to the Sophia Children's Hospital between 1970 and 1992 to analyse changes over time in the clinical presentation, diagnostic work-up, management and complications. Fifteen of these 36 children (42%) were less than 1 year old. Fever (97%) and respiratory distress (83%) were the most common symptoms at the initial presentation. Chest X-ray findings on admission or during hospitalisation included pleural effusion (75%), pneumothorax (47%), and abscess and/or pneumatocele (39%). Diagnostic and/or therapeutic thoracentesis of pleural fluid was performed in 17 of the 36 patients (47%). Twenty-one patients (58%) needed chest tube drainage. Twelve had a thoracotomy (33%). Artificial ventilation was needed in 13 of the patients (36%). Extrapulmonary complications included convulsions in 6 patients (17%) and osteomyelitis in 2 children (6%). The mean duration of hospitalization was 36 days. Two of the 36 children died (6%). The low mortality rate in this study may be the result of the relatively high rate of thoracotomy and of improvements in supportive treatment.

Child↗
PubMed1995

Altered immunoglobulin concentrations and light chain ratios in juvenile onset mixed connective tissue disease.

Immunological disturbances may result in altered immunoglobulin concentrations and kappa/lambda light chain (kappa/lambda) ratios. We measured the kappa/lambda ratios of total serum immunoglobulins and of polyclonal IgG, A, and M separately as well as concentrations of these immunoglobulins in fourteen patients with juvenile onset mixed connective tissue disease. When comparing the patient group with a reference group the mean serum IgG and IgA concentrations were respectively 2.98 G/L (p = 0.0012) and 0.79 G/L (p = 0.0114) higher in the group of patients with juvenile onset mixed connective tissue disease. The mean IgM concentration was 0.39 G/L (p = 0.0002) lower. The mean kappa/lambda ratios of total serum immunoglobulins, serum IgG, and serum IgA were respectively 0.20 (p = 0.0226), 0.28 (p = 0.0016) and 0.10 (p = 0.0732), higher in the group of patients with mixed connective tissue disease as compared with the reference group. Mean serum IgM kappa/lambda ratio, however, was 0.21 (p = 0.0046) lower. The alterations of the serum immunoglobulin concentrations and of the kappa/lambda ratios reflect immunological disturbances in patients with juvenile onset mixed connective tissue disease. The increased concentration of serum IgG and raised IgG kappa/lambda ratio and decreased concentration of serum IgM with decreased IgM kappa/lambda ratio indicate that the synthesis of kappa-bearing immunoglobulins mainly is affected.

Adolescent↗