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PubMed1993

Deposition patterns of aerosolized drugs within human lungs: effects of ventilatory parameters.

A mathematical model for inhaled aerosolized drugs is validated by comparisons of predicted particle deposition values with experimental data from adult subject inhalation exposure tests. The model is subsequently used to study the effects of ventilatory parameters on particle deposition patterns within the human lung. By altering breathing profiles, deposition values can be affected regarding quantity delivered and spatial location. Increased tidal volumes and breath-holding times increase deposition in the pulmonary region, while increased inspiratory flow rates increase deposition in the tracheobronchial region. Based upon fluid dynamics considerations (Reynolds numbers), an original method of partitioning the lung is also presented. The model has implications with regard to aerosol therapy, indicating that the efficacies of inhaled pharmacological drugs in the prophylaxis and treatment of airway diseases can be improved by regulating breathing profiles to deposit particles selectively at prescribed sites within the lung.

Adult↗
PubMed1999

Forced oscillation total respiratory resistance and spontaneous breathing lung resistance in COPD patients.

Forced-oscillation total respiratory resistance (Rrs) has been shown to underestimate spontaneous breathing lung resistance (RL,sb) in patients with airway obstruction, probably owing to upper airway shunting. The present study reinvestigates that relationship in seven severely obstructed chronic obstructive pulmonary disease patients using a technique that minimizes that artefact. Rrs at 8 and 16 Hz was computed for each successive forced oscillation cycle. Inspiratory and expiratory RL,sb were obtained by analysing transpulmonary pressure (Ptp) with a four-coefficient model, and compared to Rrs over the same periods. "Instantaneous" values of RL,sb were also obtained by computing the dynamic component of Ptp, and compared to simultaneous values of Rrs. In both respiratory phases, good agreement between Rrs and RL,sb was observed up to RL,sb values of approximately 15 hPa x s(-1) x L(-1) at 8 Hz and 10 hPa x s(-1) x L(-1) at 16 Hz. Instantaneous Rrs and RL,sb varied systematically during the respiratory cycle, exhibiting various amounts of flow- or volume-dependence in the seven patients; the amplitudes of their variations were significantly correlated, but Rrs was much more flow-dependent than RL,sb in three patients. Also, Rrs exceeded RL,sb at end-expiration in three instances, which could be related to expiratory flow limitation. In conclusion, total respiratory resistance is reliable up to much higher levels of airway obstruction than previously thought, provided upper airway shunting is avoided.

Adult↗
PubMed1995

Decrease in pulmonary function during bleomycin-containing combination chemotherapy for testicular cancer: not only a bleomycin effect.

This study was performed to determine the changes in pulmonary function in patients randomised to receive treatment with four cycles of bleomycin, etoposide and cisplatin (BEP) (27 patients) or with four cycles of etoposide and cisplatin (EP) (27 patients) for disseminated non-seminomatous testicular cancer. This enabled us to establish whether effects other than those due to bleomycin determined the detrimental effects of BEP on lung function assessments. Slow inspiratory vital capacity (VC), the transfer factor of the lungs for carbon monoxide (TLCO), the diffusing capacity of the alveolo-capillary membrane (Dm), the pulmonary capillary blood volume (Vc) and the transfer factor of the lungs for carbon monoxide per unit alveolar volume (KCO) were determined before and at 3 week intervals during chemotherapy. Both groups, similar in terms of factors that may influence pulmonary function, showed during therapy a significant decrease in TLCO compared with the pretreatment value. Only at the end of the therapy was a significant difference in TLCO between both groups observed. Dm diminished also significantly in both groups during treatment, but differences between both groups were not seen. VC and Vc decreased in patients receiving BEP but remained constant during treatment with EP. It can be concluded that the Dm, KCO, and the widely used TLCO are not suitable parameters to monitor specifically pulmonary toxicity induced by bleomycin as part of a multidrug regimen. However, VC and Vc appear to be proper lung function assessments which reflect specifically alterations induced by bleomycin.

Adolescent↗
PubMed1996

Head position and its effect on pulmonary function in tetraplegic patients.

To test the influence of head position on pulmonary function in tetraplegic individuals 15 subjects with chronic C4-C7 injuries participated in a one group pre-post test comparing the relationship between orthostatic position of the head (OPH) and standard pulmonary function tests (PFTs). Twelve subjects with habitual forward head posture and three with non-forward head posture performed PFTs in (1) their habitual posture, and (2) an experimental posture imposed by placement of thoracic and/or lumbar rolls behind their back. Results showed that changing head posture did not alter mid-forced expiratory flow or forced inspiratory vital capacity, but significantly affected forced vital capacity (t = 2.83; P < 0.05) and 12 s maximum voluntary ventilation (t = 2.07; P < 0.05). In cases where pulmonary function was altered by head position, the resulting performance was best in the subject's habitual posture, although no differences in resting pulmonary tests were observed between subjects with and without forward head position. These data show that temporary postural alterations affecting OPH, if not allowing sufficient time for muscular adaptation, adversely affect pulmonary function in tetraplegic patients.

Adolescent↗
PubMed2005

Noninvasive assessment of the tension-time index of inspiratory muscles at rest in obese male subjects.

OBJECTIVE: The aim of this study was to investigate the effect of excessive mechanical load caused by obesity on the inspiratory muscle performance in obese men at rest. METHODS: We therefore measure at rest spirometric flows and the noninvasive tension time index of inspiratory muscle (TTmus = PI/PImax x TI/TTOT) in eight obese male subjects (body mass index (BMI) > 30) and 10 controls. RESULTS: Spirometric flow (FEV1% pred, FVC% pred) and maximal inspiratory pressure (PImax) were significantly lower in obese subjects compared to controls (P < 0.001). The mean TTmus was significantly higher in obese subjects than in controls (0.136 +/- 0.003 vs 0.045 +/- 0.01). The increase in TTmus was primarily due to an increase in the ratio of mean inspiratory pressure to maximal inspiratory pressure (PI/PImax) and the duty cycle (TI/TTOT). We found a significant negative relationship between PImax and BMI (r = -0.74, P < 0.001), a positive correlation between TTmus and BMI (r = 0.80, P < 0.001) and a negative correlation between TTmus and forced expiratory volume in 1 s (r = -0.85, P < 0.001). CONCLUSION: Excessive mechanical load caused by obesity imposes a great burden on the inspiratory muscle, which may predispose such subjects to respiratory muscle weakness at rest.

Adult↗
PubMed1985

The maximal sniff in the assessment of diaphragm function in man.

We studied diaphragm function in a total of 64 normal subjects, who had no past or present respiratory or neuromuscular impairment. We measured transdiaphragmatic pressure (Pdi) during maximal sniffs and compared these values with Pdi during maximal static inspiratory efforts (PImax.). The range of Pdi during maximal sniffs (82-204 cm H2O) had better defined lower limits than Pdi during PImax. (16-164 cm H2O) and a higher mean value: mean +/- SD for maximal sniffs was 137 +/- 28 cm H2O and for PImax. was 90 +/- 37 cm H2O. The reproducibility of sniff Pdi was assessed in eight randomly chosen subjects over 3 days: the mean coefficient of variation was 7.2%. By comparison the coefficient of variation of Pdi during PImax. was 13.0% in seven subjects. The maximal sniff is a spontaneous manoeuvre, easily performed, repeatable without tiring, and reproducible. Its measurement provides a more reliable quantitative method for assessment of diaphragm strength, which has potential in clinical practice.

Adult↗
PubMed1990

Lack of effect of an inspiratory threshold load on plasma atrial natriuretic peptide levels.

1. After a run-in period, six healthy, recumbent, water-loaded male subjects breathed through an inspiratory threshold load for 90 min. To correct for prolonged recumbency, a similar protocol was followed on a separate control day, but without an inspiratory load. 2. A negative intrathoracic pressure of at least 30 cmH2O was required to overcome the threshold load. 3. Urine was collected every 30 min and analysed for sodium concentration. 4. Plasma samples were collected every 30 min and analysed for atrial natriuretic peptide concentration. 5. The inspiratory load had no effect on urine volume, urinary sodium excretion or plasma atrial natriuretic peptide levels.

Adult↗
PubMed2003

The effects of histamine and leukotriene receptor antagonism on nasal mannitol challenge in allergic rhinitis.

AIMS: It is unclear as to which mediators are involved in mediating the response to nasal mannitol challenge, a novel osmotic stimulus. METHODS: A double-blind, randomized, placebo-controlled, crossover design was employed. Nine patients with allergic rhinitis were randomized to receive a single-dose of desloratadine 5 mg, montelukast 10 mg or placebo, and underwent nasal mannitol challenges with nasal peak inspiratory flow recordings over 60 min. The change in peak nasal inspiratory flow was calculated as percentage change from baseline as the peak response and area under the time-response curve (AUC). RESULTS: Desloratadine and montelukast conferred a significant degree of protection compared to placebo for peak and AUC response, but there were no significant differences between the two drugs. For the peak response as percentage fall, the mean difference (95% CI) vs placebo was 27.7 (8.0, 47.4)% for desloratadine and 17.6 (1.9, 33.3)% for montelukast. CONCLUSIONS: Our results suggest that histamine and cysteinyl-leukotrienes are involved in mediating the response to nasal mannitol in allergic rhinitis.

Acetates↗
PubMed2000

Evaluation of treatment response in patients with seasonal allergic rhinitis using domiciliary nasal peak inspiratory flow.

BACKGROUND: Measurement of domiciliary nasal peak inspiratory flow rate (PIFR) may have a role in the objective assessment of treatment response in seasonal allergic rhinitis (SAR). OBJECTIVE: We wished to evaluate the relationship between domiciliary measurement of nasal PIFR and a variety of symptoms associated with rhinitis. METHODS: Thirty-eight nonasthmatic patients, mean age (SEM) 30 years (1.4), with symptomatic SAR were evaluated in a placebo-controlled, single-blind, double-dummy, three way parallel group study. Patients received oral cetirizine 10 mg once daily and were randomized to receive, in addition, either: (i) intranasal mometasone furoate 200 microgram (n = 14); (ii) oral montelukast 10 mg (n = 11); or (iii) placebo (n = 13). All treatments were given once daily for 4 weeks and were preceded by a 1 week placebo period. Domiciliary diary cards were used to record morning (am) and evening (pm) domiciliary nasal PIFR and symptom (nasal, eye, throat) scores and impact on daily activity. A total daily symptom score was then calculated from the sum of these separate symptom scores. RESULTS: Baseline values for symptom scores and PIFR after placebo run-in were not significantly different when comparing the three groups. After 4 weeks of active treatment, there were significant (P < 0.05) improvements in nasal symptoms, total daily symptoms and PIFR with all treatments, with there being no significant confounding effect of pollen count, when analysed as a covariate. There were significant (P < 0.01) correlations for nasal symptom scores vs PIFRam (r = - 0.51) and PIFRpm (r = - 0.56), and similarly for daily activity vs PIFRam (r = - 0.42) and PIFRpm (r = - 0.48). CONCLUSIONS: These results suggest that domiciliary measurements of nasal peak flow correlate significantly with symptoms of seasonal allergic rhinitis and may therefore be a potentially useful objective short-term marker of treatment response.

Acetates↗
PubMed2000

Nasal hyperosmolar challenge with a dry powder of mannitol in patients with allergic rhinitis. Evidence for epithelial cell involvement.

BACKGROUND: The responses to airway hyperosmolar challenges probably involve various inflammatory mediators. However, it is not fully understood which cell type/types are the source of these mediators. Potential cell types include mast cell, epithelial cell and the sensory c-fibre nerve cell. OBJECTIVE: To clarify which cell types are involved with the mediator response to hyperosmolarity in the human airway. METHODS: Ten healthy subjects, 11 patients with nonactive allergic rhinitis, and nine with active allergic rhinitis were challenged intranasally with mannitol powder, and with sham provocation, on separate days. Symptoms were assessed by visual analogue scales and nasal patency by measuring the nasal peak inspiratory flow (nPIF). Nasal lavage fluid levels of alpha(2)-macroglobulin (an index of plasma extravasation), substance P (an index of sensory nerve cell activation), tryptase (an index of mast cell activation) and 15-hydroxyeicosatetraenoic acid (15-HETE, an index of epithelial cell activation) were analysed. RESULTS: Immediate, although transient burning was the most prominent symptom in all groups whereas only the patients with active rhinitis experienced a fall in nPIF. Mannitol significantly increased the nasal lavage fluid 15-HETE levels in the allergic patients (P < 0.01 vs the sham challenge), but not in the healthy subjects. The increase in 15-HETE correlated with nasal symptoms for itching (r(s) = 0.65, P = 0.019) and burning (r(s) = 0.72, P = 0.009). Detectable levels of tryptase was found only in five allergic subjects. Lavage levels of substance P and alpha(2)-macroglobulin did not not change. CONCLUSION: Epithelial cell seems to be involved with the mediator response to airway hyperosmolar challenge. The roles of sensory c-fibre nerve cell and mast cell remained less clear.

Adult↗
PubMed2001

An open audit of montelukast, a leukotriene receptor antagonist, in nasal polyposis associated with asthma.

BACKGROUND: Nasal polyposis occurs frequently in patients with intrinsic asthma, especially in those who are aspirin sensitive. It can be difficult to treat effectively, even with surgery and regular topical intranasal corticosteroids many patients are still symptomatic. OBJECTIVE: To investigate the response to montelukast, a leukotriene D4 receptor antagonist, as an add-on therapy to topical and inhaled corticosteroids in patients, both aspirin sensitive (AS) and aspirin tolerant (AT), with nasal polyposis and asthma. METHODS: Nasal polyposis symptoms were assessed by visual analogue scales; nasal polyps were assessed by nasendoscopy and via the measurement of nasal volumes by acoustic rhinometry. The nasal airway was assessed by nasal inspiratory peakflow (NIPF). Asthma was monitored using symptom scores and peak expiratory flow measurements. Aspirin sensitivity was assessed by history together with intranasal lysine aspirin challenge. Upper and lower airway nitric oxide measurements were made before and during treatment. RESULTS: Clinical subjective improvement in nasal polyposis occurred in 64% AT (P < 0.01), patients and 50% AS patients (P > 0.05); asthma improvement in 87% AT and 61% AS patients (P < 0.05 for both). Objective changes in peak flow occurred only in AT patients (P < 0.05). Acoustic rhinometry, nasal inspiratory peak flow and nitric oxide levels did not change significantly in any group, however, correlations were seen between nitric oxide levels and polyp scores and between nitric oxide levels and acoustic rhinometry changes. Improvement on montelukast therapy was not associated with any of the following variables: age, sex, skin prick test positivity, disease duration or aspirin sensitivity. (P > 0.05 for all). CONCLUSION: The findings are consistent with a subgroup of nasal polyps/asthma patients in whom leukotriene receptor antagonists are effective. This is not related to aspirin sensitivity. Further placebo-controlled studies need to be undertaken.

Acetates↗
PubMed2000

Prevalence of sleepiness and its relation to autonomic evidence of arousals and increased inspiratory effort in a community based population of men and women.

Degrees of sleep apnoea and daytime sleepiness are quite common in community populations. However the relationship between the two is poor, although sleepiness does correlate better with a history of snoring. It has been suggested that sleep can be fragmented by upper airways obstructive events, short of full apnoeas or hypopnoeas, and that these events may not provoke full cortical arousal, but be detectable through activation of the autonomic system. Failure to detect both these could mask a relationship between 'sleep apnoea' and daytime sleepiness. We have therefore measured sleepiness (Epworth Sleepiness Scale) in addition to both autonomic 'arousals' and inspiratory effort (using pulse transit time) in 473 men and women at home. Although sleepiness was related to a history of snoring, it was not significantly predicted by the measures of autonomic 'arousal', or inspiratory effort. Reported snoring and objectively measured snoring correlated poorly. As in other studies, nocturnal hypoxic dips were correlated with obesity, age, alcohol consumption, drug usage and a history of snoring. These data make it unlikely that sleep fragmentation from subtle variants of sleep apnoea and 'autonomic' (or 'subcortical') arousals are an important source of daytime sleepiness in the community.

Arousal↗
PubMed2000

Flow-volume curve changes in patients with obstructive sleep apnoea and brief upper airway dysfunction.

OBJECTIVE: Patients with obstructive sleep apnoea (OSA) and those with brief upper airway dysfunction (BUAD) have been reported to have abnormalities of maximal flow-volume curves. This study was designed to assess the ability of flow-volume curves to predict the presence of OSA or BUAD. METHODOLOGY: Four maximal flow-volume manoeuvres performed by 33 OSA patients and 16 BUAD patients were compared with those of 36 normal subjects. Flow-volume indices, their variability, saw-toothing in the curve and an algorithm based on the flow ratios and shape of the curves were assessed. RESULTS: When the confounding factors, body mass index (BMI), age, gender and smoking status were taken into account, there was no significant difference in a variety of indices derived from the flow-volume curves between OSA and normal subjects. No BUAD patient had normal flow-volume curves as determined with the algorithm. After BMI, age, gender and smoking status were accounted for, decreased forced expiratory volume in 1 s (FEV1), and increased variability of peak expiratory flow (PEF)/peak inspiratory flow (PIF) and FEV1/PEF remained significantly associated with BUAD. CONCLUSIONS: These findings suggest that flow-volume curve indices have no value in predicting OSA. Some abnormalities are found in patients with BUAD; a normal flow-volume curve makes the diagnosis of BUAD unlikely.

Adult↗
PubMed2000

Characterization of the inspiratory manoeuvre when asthmatics inhale through a Turbohaler pre- and post-counselling in a community pharmacy.

Dose emission from a Turbohaler has been shown to be dependent on the rate of inhalation, with an optimal flow of 60 l min(-1) recommended. Some patients may need counselling to achieve this fast inhalation. Inhalation rate profiles of 24 asthmatics were measured when they inhaled through a placebo Turbohaler. The setting was a community pharmacy when the asthmatics came to collect their next supply of medication. Profiles were measured before and after counselling on how to use the Turbohaler. The mean (SD) peak inhalation rate through the Turbohaler pre- and post-counselling was 48.0 (16.8) and 54.7 (17.6) l min(-1), and their inspiratory volume was 1.75 (0.68) and 1.94 (0.62) l, respectively. Their mean (SD) percent predicted FEV1 was 57.0 (18.9)%. After counselling, 12 patients achieved an inhalation rate of > 60 l min(-1) and a further four obtained > 55 l min(-1). Emphasis should be placed on counselling patients prescribed all types of inhaled devices rather than concentrating on metered dose inhalers.

Administration, Inhalation↗
PubMed2000

Maximal inspiratory mouth pressures (PIMAX) in healthy subjects--what is the lower limit of normal?

BACKGROUND: Maximal inspiratory mouth pressures are suitable for non-invasive evaluation of respiratory muscle function. Different studies on PIMAX give predicted normal values and their relation to anthropometric data. Due to a large inter-subject variation of PIMAX, predicted values, however, maximal inspiratory mouth pressures are not suitable to define the individual expected normal PIMAX. What is the lower limit of the normal range? METHODS: PIMAX has been prospectively measured in a representative sample of 504 healthy volunteers (248 males and 256 females) between 18 and 82 years of age with normal lung function. Age, height, weight, body mass index (BMI) and smoking status were recorded and incorporated stepwise in a multiple regression analysis to determine prediction equations. Lower limits of the normal range were defined as the fifth percentile of the residuals derived from the regression model. RESULTS: Mean values of PIMAX were 9.95 kPa for men and 7.43 kPa for women. Significant correlations were found with height, weight, BMI, FEV1, PEF and FVC (P<0.01). The strongest correlation appeared with sex and age (P<0.001). Smoking status and smoked pack-years were not independent predictors of inspiratory pressures. Lower limits of normal were 59% for women and 60% for men of the predicted PIMAX. CONCLUSIONS: In the interpretation of maximal inspiratory mouth pressures, normal values should represent the lower limit of the normal range derived from the regression model in order to avoid false pathological results. Prediction equations as well as lower limits of normal resulting from a study cohort of healthy 18-82-year-olds are given and are recommended to be used by pulmonary function laboratories in young and old patients.

Adolescent↗
PubMed2003

Reproducibility of forced inspiratory and expiratory volumes after bronchodilation in patients with COPD or asthma.

The aim of the present study was to assess the reproducibility of changes in forced inspiratory volumes after bronchodilator inhalation. Thirteen patients with chronic obstructive pulmonary disease (COPD) (FEV1, 32-75%pred) and 10 patients with asthma (FEV1, 43-75%pred) inhaled either 200 microg fenoterol or 200 microg oxitropium bromide or placebo, each of them on three occasions, on nine different days in a randomised, cross-over, double-blind fashion. Forced expiratory (FEV1) and inspiratory (FIV1) volumes were measured before and 30 min after inhalation. In patients with COPD, the increase in FEV1 (coefficient of variation) was 221 ml (43%) after fenoterol and 235 ml (33%) after oxitropium; changes in FIV1 were 301 ml (45%) and 360 ml (29%). In patients with asthma, FEV1 improved by 618 ml (26%) and 482 ml (25%), FIV1 by 553 ml (41%) and 475 ml (23%). In less severe COPD or asthma, the reduction in dyspnoea was associated with the improvements in both FIV1 and FEV1, but in severe COPD with the improvement in FIV1 only. The data demonstrate that, at least in terms of relative changes, the reproducibility of bronchodilator responses in terms of FIV1 is similar to that of FEV1 and they underline the assertion of FIV1 being a sensible parameter particularly in severe COPD.

Adrenergic beta-Agonists↗
PubMed2003

Peak inspiratory flow through diskus and turbuhaler, measured by means of a peak inspiratory flow meter (In-Check DIAL).

With a handheld peak inspiratory flow (PIF) meter (In-Check DIAL), the internal resistance of the Diskus (DKR) and the Turbuhaler (THR) can be simulated by means of calibrated resistances. This study investigated whether patients with asthma or chronic obstructive pulmonary disease could generate a PIF which is optimal for the Diskus (DK) (30 l/min) and theTurbuhaler (TH) (60 l/min). Peak expiratory flow (PEF) and maximal inspiratory pressure (MIP) were also assessed. All 50 patients (30 males, mean age 56.9) achieved the required flow of 30 l/min with the DKR, while six patients (five females) could not generate the optimal flow of 60 l/min via theTHR. Analysis showed that MIP was an independent predictor of an adequate PIF through theTHR. During the study eight patients were treated for an exacerbation of which four could not generate an adequate PIF via the THR. Analysis showed that the female gender and an exacerbation appeared to be independent predictors of the inability to generate an adequate PIF via the THR. Twelve per cent of patients (25% of females) could not generate the optimal inspiratory flow via the THR. When in doubt whether the patient can generate an adequate inspiration, measurement with the In-Check DIAL is recommended.

Asthma↗
PubMed2002

Sleep abnormalities associated with neuromuscular disease: pathophysiology and evaluation.

The development of respiratory failure is common in patients with neuromuscular disorders that involve the respiratory muscles. However, the high incidence of sleep-related breathing problems in this population is less well known. In patients with neuromuscular disease, nocturnal breathing abnormalities frequently precede respiratory failure during wakefulness by months or even years. These nocturnal breathing problems are caused by multiple factors, including diaphragm and upper airway muscle weakness, scoliosis, obesity, and central respiratory control problems. Advances in the understanding of the links between sleep-disordered breathing and the development of daytime dysfunction and respiratory failure has revolutionized the management of these individuals. Mask positive pressure therapy is now available to improve both quality of life and longevity for these individuals. The lack of correlation between daytime testing and the severity of nocturnal breathing abnormalities makes it difficult to predict the presence of sleep-disordered breathing. Further, patients may not always be aware of symptoms associated with sleep-disordered breathing, even if specifically questioned. However, simple bedside measurements of vital capacity and inspiratory muscle strength can provide useful guides for when nocturnal respiratory monitoring is indicated.

Journal Article↗