Kirsi Kontra - Academia.edu (original) (raw)

Papers by Kirsi Kontra

Pharmaceutica Acta Helvetiae

American Journal of Health-System Pharmacy

The clinical respiratory journal, 2013

Asthma control and quality of life are poorly associated with traditional asthma biomarkers. In t... more Asthma control and quality of life are poorly associated with traditional asthma biomarkers. In the present study, we evaluated two new cough provocation tests in this respect. Asthma Control Questionnaire and Leicester Cough Questionnaire were completed by 36 stable asthmatics. Cough provocation tests with hypertonic saline and isocapnic hyperpnoea of dry air were performed, as well as spirometry, ambulatory peak expiratory flow (PEF) monitoring and exhaled nitric oxide (eNO) measurement. Leicester Cough Questionnaire score correlated closely with cough responsiveness to hypertonic saline and isocapnic hyperpnoea (R = -0.66, P < 0.001 and R = -0.49, P = 0.002, respectively). Asthma Control Questionnaire score also correlated with the cough responsiveness to these tests (R = 0.52, P = 0.001 and R = 0.43, P = 0.008, respectively). Forced expiratory volume in 1 s (%predicted), diurnal PEF variation and eNO did not correlate with cough-related quality of life but showed some associa...

Journal of opioid management

The purpose of the study was to investigate whether or not compliance monitoring by microchip cou... more The purpose of the study was to investigate whether or not compliance monitoring by microchip could offer a feasible method for reducing abuse and/or diversion of medication from unsupervised substitution treatment for opioid addiction. Naturalistic, 4-week pilot study in out patients. All our patients (N = 12) on buprenorphine-naloxone combination (Suboxone) received their medication for 6 days in a compliance-monitoring device (PharmaDDSi, StoraEnso), which registers date and time of tablet removal. Patients were instructed to take all tablets as one dose. Time cues were displayed and discussed with the patients during their weekly visits for supervised drug administration and counseling. Regularity of registered time cues, treatment costs in comparison with routine treatment, patients' answers from a questionnaire on acceptability, and effect on drug diversion. Six patients showed good compliance, in two patients irregularities were minor, but in two others lack of adherence ...

Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition

Hepatobiliary complications are common during parenteral nutrition. Lipid moiety in commercially ... more Hepatobiliary complications are common during parenteral nutrition. Lipid moiety in commercially available solutions contains plant sterols. It is not known whether plant sterols in parenteral nutrition interfere with hepatic function in adults. We detected how different amounts of plant sterols in parenteral nutrition solution affected serum plant sterol concentrations and liver enzymes during a 1.5-year follow-up in a patient with short bowel syndrome. Serum lipid, plant sterol, and liver enzyme levels were measured regularly during the transition from Intralipid (100% soy-based intravenous fat emulsion) to ClinOleic (an olive oil-based intravenous fat emulsion with 80% olive oil, 20% soy oil and lower plant sterols); the lipid supply was also gradually increased from 20 to 35 g/d. Plant sterols in parenteral nutrition solution and serum were measured with gas-liquid chromatography. During infusion of soy-based intravenous fat emulsion (30 g/d, total plant sterols 87 mg/d), the co...

Chest, 2005

To analyze the cough response to three airway challenges in order to clarify whether the recordin... more To analyze the cough response to three airway challenges in order to clarify whether the recording of the provoked coughs would be beneficial in the management of asthma. A prospective study. University hospital. Fifteen healthy subjects, 16 steroid-naïve subjects with asthma, and 16 subjects with steroid-treated asthma. Inhalation challenges with isotonic histamine, hypertonic saline solution, and hypertonic histamine, using an ultrasonic nebulizer and 2-min tidal breathing method. Airflow parameters were measured with a spirometer, and the coughs were recorded manually. Coughing during the isotonic histamine challenge was associated with the degree of the bronchoconstriction induced. When this was taken into account, the healthy subjects coughed as frequently as the asthmatic subjects. During the two hypertonic challenges, the asthmatic subjects coughed more frequently than did the healthy subjects when the induced bronchoconstriction had not yet developed. At that stage of the hy...

Respiratory medicine, 2005

There is significant overlap in the responsiveness to direct airway challenges, such as the hista... more There is significant overlap in the responsiveness to direct airway challenges, such as the histamine challenge, between asthmatic and non-asthmatic subjects, which decreases their accuracy in the diagnosis of asthma. To minimise this overlap, a new test, hypertonic histamine challenge, was developed. Fifteen healthy subjects, 16 subjects with steroid-naive asthma, and 16 asthmatic subjects undergoing inhaled corticosteroid treatment underwent inhalation challenges with hypertonic saline, isotonic histamine, and hypertonic histamine, using an ultrasonic nebuliser and 2-min tidal breathing method. The increase in histamine solution tonicity decreased the histamine PC20 values only in the steroid-naive asthmatic subjects (1.1 (0.5-2.7) vs. 0.5 (0.2-1.2) mg/ml, P = 0.047). Using 1mg/ml as the cut-off value, the sensitivity, specificity, and accuracy of the hypertonic histamine challenge to detect steroid-naive asthma was 81%, 100%, and 90%. The respective values for the isotonic histam...

The Clinical Respiratory Journal, 2010

Background and Aims: Bronchial provocation tests may be utilised to monitor the efficacy of the c... more Background and Aims: Bronchial provocation tests may be utilised to monitor the efficacy of the corticosteroid treatment. Unfortunately, these measurements necessitate good patient cooperation during the spirometry. Coughing during such tests is related to the degree of the bronchoconstriction and occurs involuntarily, i.e. independent of patient cooperation. This study aimed to evaluate the utility of a hypertonic histamine challenge-induced cough in assessing the efficacy of inhaled corticosteroid treatment. Methods: A total of 16 steroid-naïve asthmatics and 10 non-asthmatic, symptomatic controls received 800-mg beclomethasone (Beclomet Easyhaler®, Orion Ltd., Orion Pharma, Helsinki, Finland) via powder inhaler per day for 8 weeks. Videoed inhalation challenge with hypertonic histamine solution was performed before and after the treatment. Symptom questionnaire was completed before both challenges. The airway responsiveness to hypertonic histamine was expressed as the cumulative number of coughs divided by the final histamine concentration administered [coughs/concentration ratio (CCR)] and as the provocative concentration of histamine to induce a 20% fall in FEV1 (PC20). Results: CCR [geometric mean; 95% confidence interval (CI)] of the asthmatic subjects decreased from 494 (209-1168) to 73.6 (29.8-182) coughs per mg/mL (P = 0.002). Their PC20 levels were 1.31 (1.07-1.60) and 1.91 (1.33-2.74) mg/mL over the treatment period (P = 0.01). The symptom frequency also decreased significantly in the asthmatics (P = 0.039). There were no significant changes in PC20 level, in CCR level or in symptom frequency in non-asthmatic subjects during the treatment. Conclusions: Hypertonic histamine challenge-induced cough and PC20 are sensitive measures in assessing the treatment effect in asthma. The cough response may be especially useful in subjects who cannot perform spirometry reliably.

Respiratory Medicine, 2008

Airway responses to bronchial provocation tests are traditionally assessed with spirometry which ... more Airway responses to bronchial provocation tests are traditionally assessed with spirometry which necessitates considerable patient co-operation. It has been shown that coughing during bronchial provocation tests is related to the degree of bronchoconstriction which, in turn, is independent of patient co-operation. The aim of the present study was to evaluate the utility of coughing induced by the hypertonic histamine challenge in the differential diagnosis of asthma in a clinically relevant patient population.

Journal of Clinical Pharmacy and Therapeutics, 2007

To compare content uniformities between different sizes of extemporaneously compounded nifedipine... more To compare content uniformities between different sizes of extemporaneously compounded nifedipine oral powders and capsules, in order to find out if capsules could be used instead of oral powders as paediatric medications. Actual content and content uniformity of extemporaneously compounded 1-mg nifedipine oral powders and capsules were evaluated by a high performance liquid chromatographic assay. Capsules and powders were prepared by triturating 10-mg nifedipine tablets with different amounts of lactose or microcrystalline cellulose with a mortar and pestle using a standard geometric dilution technique. Oral powders were weighed individually and capsules were filled by a hand-operated capsule-filling machine. Four different sizes of powders (500, 300, 100 and 50 mg) and three different sizes of capsules (numbers 1, 3 and 4) were prepared. Ten oral powders and 10 capsules from each batch were randomly selected and individually assayed for nifedipine amount. The extemporaneously prepared nifedipine oral powders and capsules were within acceptable limits for content uniformity, as defined by the European Pharmacopoeia, but the results indicate that the loss of nifedipine during the preparation process may be considerable for both preparations. The concentration on nifedipine decreased while the total mass of the oral powder decreased. These results demonstrate that nifedipine oral powders can be replaced by capsules, whose contents are emptied for use, in paediatric medications. Compounding small capsules, such as size number 3 or 4, is acceptable when considering the average drug content. The total weight of the oral powder should be at least 300 mg. The preparation of nifedipine in all studied capsule sizes was safe with either lactose monohydrate or microcrystalline cellulose as excipients. Thus, emptied capsules seem to be a good choice for delivering a paediatric medication. The loss of nifedipine was considerable in oral powders with low total weight.

Journal of Clinical Pharmacy and Therapeutics, 2001

To formulate an oral suspension of nifedipine for paediatric use and to assess its content unifor... more To formulate an oral suspension of nifedipine for paediatric use and to assess its content uniformity as well as the microbiological and physical stabilities of the hypromellose solution that was used in the formulation. Six concentrations (0.5-3.0%) of hypromellose colloids and water as a blank were compounded with nifedipine, both as a powder and as crushed tablets, to a concentration of 1 mg/mL. Four different screening tests were used to find the most homogenous and dose-accurate combination. First, nifedipine suspensions were stored in vials for one month and visual homogenity of the redispersed suspensions was observed. Second, the homogenity of the suspensions was studied by measuring the nifedipine concentration from upper, middle and lower parts of the redispersed suspension. Next, the nifedipine concentration was measured from the suspensions immediately, 1 min and 2 min after shaking to ensure dose accuracy during the administration period. Finally, suspensions were packaged into oral disposable syringes and nifedipine concentrations were determined after one month of storage. Content uniformity of the packaged single-dose syringe suspensions was studied according to a method established by the European Pharmacopoeia. Microbiological stability, density, pH, osmolality, viscosity and surface tension of the hypromellose solution were studied over a 12-month storage period. From the results of the screening tests of hypromellose solution, 1.0% hypromellose was chosen as the vehicle for nifedipine enteral suspensions, made from both crushed tablets and nifedipine powder. Nifedipine suspensions made from hypromellose 1.0% were easiest to redisperse as a homogenous solution, and it also appeared best on visual inspection. The content uniformity of the suspension complied with the test recommended by the European Pharmacopoeia. The 1.0% hypromellose solution was found to be microbiologically stable for 6 months and physically stable for 12 months.

Agents and Actions, 1990

The effects of famotidine (40 mg), ranitidine (300 mg) and sodium citrate (30 ml) on the gastric ... more The effects of famotidine (40 mg), ranitidine (300 mg) and sodium citrate (30 ml) on the gastric pH and volume were tested in 114 patients undergoing upper abdominal surgery. Gastric content was aspirated through a multiorifice tube immediately after intubation, at the end of operation and after a recovery room period of one hour. All three drug regimens significantly increased the mean gastric pH value compared with the control group. Famotidine and ranitidine reduced the volume of gastric content in comparison with sodium citrate and the control group. However, the difference was significant only in the recovery room sample.

Cough, 2011

Background: Mechanisms behind asthmatic cough are largely unknown. It is known that hyperosmolar ... more Background: Mechanisms behind asthmatic cough are largely unknown. It is known that hyperosmolar challenges provoke cough in asthmatic but not in the healthy subjects. It has been postulated that isocapnic hyperpnea of dry air (IHDA) and hypertonic aerosols act via similar mechanisms in asthma to cause bronchoconstriction. We investigated whether there is an association between cough response induced by IHDA and hypertonic saline (HS) challenges. Methods: Thirty-six asthmatic and 14 healthy subjects inhaled HS solutions with increasing osmolalities administered via ultrasonic nebuliser until 15 cumulative coughs were recorded. The IHDA consisted of three threeminute ventilation steps: 30%, 60% and 100% of maximal voluntary ventilation with an end-point of 30 cumulative coughs. The challenges were performed on separate days at least 48 hours between them and within one week. Inhaled salbutamol (400 mcg) was administered before the challenges to prevent bronchoconstriction. The cough response was expressed as the cough-to-dose ratio (CDR) which is the total number of coughs divided by the maximal osmolality inhaled or the maximal ventilation achieved. Results: Cough response to IHDA correlated with the HS challenge (Rs = 0.59, p < 0.001). Cough response to IHDA was at its strongest during the first minute after the challenge. IHDA induced more cough among asthmatic than healthy subjects CDR being (mean ± SD) 0.464 ± 0.514 and 0.011 ± 0.024 coughs/MVV%, p < 0.001, respectively. Salbutamol effectively prevented bronchoconstriction to both challenges. Conclusions: Asthmatic patients are hypersensitive to the cough-provoking effect of hyperpnoea, as they are to hypertonicity. Cough response induced by IHDA and HS correlated well suggesting similar mechanisms behind the responses.

Clinical & Experimental Allergy, 2008

Cough is one of the most common symptoms of asthma. However, studies using capsaicin, citric acid... more Cough is one of the most common symptoms of asthma. However, studies using capsaicin, citric acid, or tartaric acid to document cough threshold have repeatedly failed to show statistically significant differences between asthmatic and healthy subjects. The studies using hypertonic aerosols as the cough stimulant have suggested an enhanced sensitivity in asthmatic subjects but the induced bronchoconstriction has made the interpretation of the results difficult. To determine the cough sensitivity to hypertonicity in healthy subjects, patients with chronic cough, and patients with asthma in a setting where the induction of bronchoconstriction is prevented. Nineteen healthy subjects, 21 non-asthmatic patients with chronic cough, and 26 asthmatic patients with chronic cough underwent an incremental hypertonic saline challenge including a pre-treatment with 0.4 mg of salbutamol. Spirometry was performed before the challenge, after salbutamol, and after the challenge. The patients with cough also underwent skin testing, histamine challenge, exhaled nitric oxide measurement, ambulatory peak flow monitoring, kept cough diary, and filled in the Leicester Cough Questionnaire. Eighteen patients repeated the saline challenge. The challenge did not induce bronchoconstriction in any group. The osmolality to provoke 15 cumulative coughs was significantly smaller in the asthmatic patients than in the healthy subjects (P<0.001) and in the cough patients without asthma (P=0.04). According to multivariate analysis among all the 47 patients with cough, female sex (P<0.001) and large spontaneous peak flow variation in the ambulatory recording (P=0.001) were associated with high sensitivity to saline. The saline challenge response was well repeatable (intraclass correlation coefficient 0.90). The findings of the present study are not affected by induced bronchoconstriction. Asthma or, more specifically, spontaneous, reversible airway obstruction is associated with an enhanced sensitivity to the cough-provoking effect of hypertonic saline. This suggests a pathological function of the sensorineural apparatus in this disorder.

The Clinical Respiratory Journal, 2007

Introduction: Although classical asthma is associated with airway hyperresponsiveness (AHR), this... more Introduction: Although classical asthma is associated with airway hyperresponsiveness (AHR), this condition is also present in many cardiopulmonary disorders undermining the rational basis of its measurement in the differential diagnosis of asthma. We have recently introduced a new method to investigate AHR, the hypertonic histamine challenge (HHC). Objective: The aim of this study was to evaluate the differential diagnostic power of HHC in a clinically representative sample of 138 patients. Methods: Fifty-seven patients from the outpatient clinic of the authors' hospital with symptoms indicative of asthma were consecutively recruited. Asthma was confirmed in 31 subjects. The remaining 26 subjects formed the control group, in conjunction with seven patients with COPD, 15 patients with interstitial lung disease, 21 patients with rhinitis, 13 patients with heart failure and 25 healthy controls. Hypertonic histamine solution was administered with an ultrasonic nebuliser. Results: Only the PC20 values of asthmatic subjects differed statistically significantly from those of the healthy group (P < 0.0001). The receiver operator characteristic curve indicated that a PC20 value of 0.83 mg/mL would be the optimal cut-off point of HHC to separate the asthmatics from the symptomatic controls with a sensitivity of 81% and specificity of 70%. With the PC20 values of 0.1 and 4.0 mg/mL, the sensitivities were 42% and 100%, and the specificities were 96% and 40%, respectively. In these limits, HHC either confirmed or excluded asthma in 64 out of 138 patients (46%). Conclusion: The authors' attempt to improve the accuracy of the airway challenge test by combining direct and indirect challenges did not overcome the diagnostic limitations of previously utilised airway challenges. Please cite this paper as: Purokivi M, Koskela HO, Koistinen T, Magga J, Peuhkurinen K, Kiviniemi V and Kontra KM. Utility of hypertonic histamine challenge in distinguishing difficult-to-diagnose asthma. The Clinical Respiratory Journal 2007; 1: 91-98.