A longitudinal study of changes in respiratory status in young adults, 1993-2001.

SETTING: There is little information regarding the prognosis of respiratory symptoms in early adulthood or the effects of potential risk factors. OBJECTIVE: To observe changing respiratory morbidity in a group of young adults over a period of 6-8 years. DESIGN: Subjects responding to three or more consecutive postal respiratory surveys carried out between 1993 and 2001 were included in the study. In addition to asthma (defined by a validated scoring system), two symptoms were examined: wheeze and being woken by cough. Five outcomes were defined: persistent, remission, new onset, never and intermittent. RESULTS: Of 2693 subjects who responded to at least one survey, about one third were eligible for inclusion: 10.2% reported wheeze at each survey (persistent) and 3.6% had persistent asthma. Persistent wheeze was seen in almost half (46.7%) of those reporting the symptom at their first survey. The corresponding figure for asthma was 32%. New onset wheeze was found in 16.2% of subjects without wheeze at baseline (asthma 9.7%). Smoking was significantly associated with new onset wheeze (OR 1.97, 95% CI 1.30-3.00) and asthma (OR 2.14, 95% CI 1.26-3.50), but not with persistent symptoms. CONCLUSION: These findings highlight the importance of policies to reduce smoking prevalence in young adults, and will help in the planning of future health care.

Endotoxin exposure in asthmatic children and matched healthy controls: results of IPEADAM study.

UNLABELLED: Children spend increasing time indoors. Exposure to environmental factors may contribute to the development or exacerbation of the asthmatic phenotype. Inter-relationships between these factors might influence the manifestation of asthma. Endotoxin exposure has been shown to have pro-inflammatory and protective effects in different situations. We investigated the exposure to several indoor pollutants (endotoxin, Der p 1, damp, ETS, PM2.5) in asthmatic and healthy children. The children were recruited from two primary care centers according to their response to a validated questionnaire. Asthmatic children were matched for sex, age and sib-ship size with children living in asthma free households. Of 90 matched pairs, higher levels of endotoxin were found in the living room carpets, but not the bedroom carpet or mattresses of the asthma compared with the control homes (STATA analysis OR: 1.88 (1.11-3.18); P=0.018). Asthmatic children were also more likely to live as part of a single parent family, in a house where the parents self-reported the presence of damp, and where the living room had been redecorated in the 12 months prior to the sampling visits. This study suggests that endotoxin in urban homes is a risk factor for the development of asthma. Moreover, this study found that there were no statistically significant interactions between environmental factors. PRACTICAL IMPLICATIONS: This study has demonstrated that the home environments of English children (4-17) with asthma and without the disease do not differ greatly. With the exception of endotoxin, the parameters examined in this study, including house dust mite allergens, nitrogen dioxide, ETS and damp are unlikely to be related to the development of asthma. Avoidance of these pollutants may not be beneficial in preventing asthma in this age group.

Prevalence of respiratory symptoms in under 5s: 1993 to 2001.

AIM: To describe changes in the prevalence of respiratory symptoms in 1-4 year olds in two general practice populations observed on four occasions over an eight year period. METHODS: In 1993, 1995, 1999, and 2001, questionnaires were posted to the parents of patients aged 15 years or younger and registered with either of two general practices. Only children aged 1-4 years at time of questionnaire completion were included in this study. For each survey, the prevalence of five key variables was determined. RESULTS: The response rates for all children in the four surveys were 72.8%, 70.6%, 65.0%, and 60.7% respectively. When respondents aged 1-4 years old were stratified into one-year age bands, there was a decrease in the prevalence of symptoms over the study period. This was statistically significant for wheeze and night cough in 2 year olds and for night cough in 4 year olds. Repeated antibiotic prescriptions decreased significantly for 2 and 3 year olds. There were no changes in the prevalence of hay fever or eczema and family history of asthma. CONCLUSIONS: The downward trend in symptom prevalence might represent a real decrease in symptoms or improvements in treatment. In the absence of changes in the prevalence of hay fever and family history of asthma, the downward trend in symptom prevalence may suggest changes in the prevalence of conditions other than asthma.

Trends in smoking habits: a longitudinal population study.

BACKGROUND: In 1998, the UK government published a White Paper in which it set long-term targets for reducing smoking in the population. This longitudinal study aimed to examine whether progress has been made in achieving these in two adult general practice populations over an 8-year period. METHODS: Postal respiratory questionnaires, based on the European Community Respiratory Health Questionnaire, were sent to all patients registered with two practices in North West England on four occasions between 1993 and 2001. Two analyses were carried out. The first (smaller cohort) included only those subjects answering the question concerning current smoking on all four occasions, the second (larger cohort) those answering at least twice. RESULTS: The smaller cohort included 2403 subjects (19.6% of all respondents). Almost one-quarter reported in all four surveys that they smoked, the highest proportion being in those aged 35-44 years. The proportion of smokers decreased from 34.2% (1993) to 30.3% (2001) (P < 0.001 for trend) and the prevalence of heavy smokers fell from 15.9 to 13.3% (P < 0.001 for trend) over the same period. There were, however, no reductions in those aged <45 years in 1993. These changes were confirmed in the larger cohort which included 7274 subjects (59.3% of respondents). CONCLUSIONS: If smoking-related disease is to be reduced, it is important that adults are targeted for smoking prevention and cessation before they reach middle age. Only when such initiatives show success will smoking prevention among their children become a practical proposition.

Respiratory illness and healthcare utilization in children: the primary and secondary care interface.

The aim of the present study was to quantify the healthcare utilization of a child population according to level of respiratory illness. A stratified random sample of 713 children was selected from respondents to a postal respiratory questionnaire, carried out in two general practice populations in 1993. Children were stratified into four groups according to the number of positive responses to five key questions. These groups were used as indicators of likelihood of asthma diagnosis. A search was made of these childrens' practice records covering a 2-yr period, to include both primary and secondary healthcare. There was a significant increase across positive response groups in the proportion of children having primary and secondary care based consultations, particularly for respiratory conditions (p = 0.001). There was also a significant increase in prescribing. Of those children considered to be "likely asthmatics" from their questionnaire responses, 8.1% (n = 31) did not receive any primary or secondary care for a respiratory problem over the 2-yr period. As the likelihood of respiratory illness increased in this population, more demand was made upon resources for the treatment of respiratory illness. Quantification of this demand enables evidence based resource allocation decisions to be made. This method of quantification could be applied in other populations.

Using a neural network to screen a population for asthma.

PURPOSE: To use a neural network to rank a population according to individual likelihood of asthma based on their responses to a respiratory questionnaire. METHODS: A final diagnosis of asthma can be made only after full clinical assessment but limited resources make it impossible to offer this to complete populations as part of a screening programme. Prioritisation is required so that review can be offered most promptly to those most in need. A stratified random sample of 180 from 6825 respondents to a community survey underwent clinical review. They were categorised according to likelihood of asthma by three independent experts whose opinions were combined into a single probability label for each patient. A neural network was trained to relate questionnaire responses to probability labels. The trained network was applied to the whole community to produce a ranking order based on likelihood of asthma. A screening threshold could then be set to correspond to available resources, and patients above this level with no recorded evidence of asthma diagnosis could be assessed clinically. Using the known probability labels from the training set, it was possible to derive the expected proportion of true asthmatics in any set of patients. RESULTS: If the screening threshold had been set to capture the top 10% of the ranked population (n = 683), then 239 patients above this threshold had no evidence of diagnosis and would need assessment. Of these, it would be expected that 74% would have the diagnosis confirmed. CONCLUSIONS: This approach allows prioritisation of a population where resources for diagnostic examination are limited.

The use of a screening questionnaire to identify children with likely asthma.

BACKGROUND: The theory that airway remodeling and possible fixed asthma may result from failure to treat asthma airway inflammation highlights the importance of the early identification of patients with likely asthma. AIM: To identify children with likely asthma whose condition is unknown to the medical services. STUDY: Postal questionnaire survey. SETTING: Children in two general practice populations in 1999. METHOD: Parents completed the postal questionnaire surveys. Two validated scoring systems were used to identify children with 'likely asthma': first, three or more positive responses to five key questions; second, three or more positive responses to the same five questions and one more severe symptom (e.g. exercise-induced wheeze). Questionnaire responses were linked to practice records to determine those with a recorded diagnosis of asthma (ever) or of inhaled medication (past 12 months). RESULTS: Using the first scoring system, 22.5% of children were identified as having likely asthma; more than one-third of these (35.1%) had no corroborative evidence recorded in the practice records. With the second system, 15.5% had likely asthma, a quarter of whom had no corroborative evidence. Depending on the scoring system chosen, between 3.5% and 8% of children in these practices had likely asthma but no corroborative evidence in their records. CONCLUSIONS: Children identified using either of these scoring systems would require full clinical assessment to determine their need for medical intervention. These findings have implications for the allocation of health care resources.

Assessment of a simple scoring system applied to a screening questionnaire of asthma in children aged 5-15 yrs.

The aim of the present study was to validate a simple scoring system using a parent-completed screening questionnaire to identify children aged 5-15 yrs who may have asthma. A stratified random sample of 157 children of 1,808 whose parents had answered a postal respiratory questionnaire underwent detailed clinical evaluation. The results were reviewed by three independent paediatricians whose opinions were combined to reach, for each child, decisions regarding three standards: 1) "possible asthma" defined as >50% likelihood of having asthma; 2) "possible asthma" defined as meriting a clinical trial of asthma medication; and 3) "probable asthma" defined as >90% likelihood of having asthma. The combined decisions were compared to three sets of questionnaire scores, in order to determine the positive predictive value, sensitivity and specificity of each set in identifying children with probable/possible asthma. The three sets of chosen questionnaire scores all had positive predictive values of 79-96% for predicting possible asthma, using either the combined expert opinion ">50% likelihood of asthma" or that of "warrants a trial of treatment" as the definition. This suggests that a low proportion of false positives would be obtained were this scoring system to be used for a screening programme. The combined decision >90% chance of asthma could be used as a means of estimating prevalence of asthma in the survey. When used for this, the prevalence of asthma in the surveyed population was 18.8% (95% confidence interval 13.1-26.3). In conclusion, the present scoring system, based on a simple respiratory questionnaire, provides a valid method of identifying children likely to have asthma, and who, if unknown to the medical services, would benefit from clinical review.

Relationship between exhaled nitric oxide and childhood asthma.

The purpose of the study was to determine if exhaled nitric oxide levels in children varied according to their asthmatic and atopic status. Exhaled nitric oxide was measured in a sample of 93 children attending the North West Lung Centre, Manchester, United Kingdom, for the clinical evaluation of a respiratory questionnaire being developed as a screening tool in general practice. The clinical assessment included full lung function, skin prick testing, and exercise challenge. Children were said to be asthmatic either by consensus decision of three independent consultant pediatricians, who reviewed all the clinical results except the nitric oxide measurements, or by positive exercise test. Atopic asthmatic children had higher geometric mean exhaled nitric oxide levels (consensus decision, 12.5 ppb [parts per billion] 95% CI, 8.3 to 18. 8; positive exercise test, 12.2 ppb 95% CI, 7.6 to 19.7) than did nonatopic asthmatic children (3.2 ppb 95% CI, 2.3 to 4.6; 3.2 ppb 95% CI, 2.0 to 5.0), atopic nonasthmatic children (3.8 ppb 95% CI, 2. 7 to 5.5; 5.7 ppb 95% CI, 4.1 to 8.0), or nonatopic nonasthmatic children (3.4 ppb 95% CI, 2.8 to 4.1; 3.5 ppb 95% CI, 3.0 to 4.1). Thus, exhaled nitric oxide was raised in atopic asthmatics but not in nonatopic asthmatics, and these nonatopic asthmatics had levels of exhaled nitric oxide similar to those of the nonasthmatics whether atopic or not.

Cardiac single-photon emission tomography with a 90 degrees dual-head system.

Dual-head single-photon emission tomography (SPET) systems which permit a 90 degrees orientation of the heads provide a twofold increase in sensitivity for 180 degrees SPET compared with single-head systems. Since such systems have additional mechanical and electrical alignment and stability requirements, clinical equivalency for myocardial perfusion SPET must be demonstrated. Accordingly, we studied 26 subjects who underwent exercise thallium scintigraphy consecutively with both single-head and dual-head systems. Image acquisition was similar, except that the dual-head study took one-half the time. Image reconstruction was identical. Images were interpreted in a blinded fashion, and rated for technical quality. All 26 studies were equivalently interpreted for the presence or absence of perfusion defects. Fourteen of the studies were judged to be technically equivalent; seven were judged to be slightly better with the single-head system; three were judged to be slightly better with the dual-head system; and two were judged to be definitely better with the dual-head system. We conclude that dual-head 90 degrees systems provide equivalent clinical performance in half the acquisition time.

Effect of differential tracer washout during SPECT acquisition.

A central assumption in SPECT is that the projection data are "consistent," that is, the camera views an unchanging distribution during acquisition. Several new radiotracers of interest, including 99mTc-teboroxime (Cardiotec), have rapid clearance from the myocardium. Furthermore, the washout is different in normal and ischemic tissues. We used computer simulations to estimate the effect of this differential washout on quantification of the severity of ischemia. We simulated defect-to-normal myocardial activity ratios of 1 (no defect), 0.8, 0.6, 0.4, 0.2, and 0 (complete defect), with single defects placed either in the lateral wall or apex, and SPECT acquisitions of 1, 3, 6, 12, and 24 total minutes. We modeled washout with a monoexponential curve whose clearance half-time was 5.9 min for "normal myocardium" and 9.3 min for "ischemic myocardium." We found that differential washout from normal and ischemic zones produced image artifacts and errors in defect quantification for acquisitions longer than 3 min. With longer acquisitions, the degree of ischemia was significantly underestimated, with increasing error at longer acquisition times. In addition, in the "no defect" situation an apparent small lateral wall defect (relative to the apex) was present. Finally, lateral wall defects produced artifacts (streaks and reduced apparent activity) in the opposite (medial) wall. Differential normal/ischemic zone washout during SPECT acquisition produces artifacts and errors in quantification, whose severity is dependent on acquisition length, actual defect severity, and defect location.

Tomographic myocardial perfusion imaging with technetium-99m-teboroxime at rest and after dipyridamole.

This study was done to determine whether the rapidly clearing myocardial perfusion agent 99mTc-teboroxime (SQ 30217, Cardiotec) could be combined with tomographic imaging to accurately quantify regional myocardial blood flow distribution in anesthetized dogs. Following stenosis of the anterior descending (LAD, n = 10) or circumflex (LCX, n = 5) coronary arteries, teboroxime was administered simultaneously with radioactive microspheres, at rest and following infusion of dipyridamole (0.15 mg/kg/min x 4 min). Tomographic imaging began 1 min after each teboroxime injection and continued for 12 min. For LAD stenosis, when the dipyridamole study was performed first, teboroxime activity in the center of the ischemic region was closely correlated with tissue microsphere content. However, the severity of the dipyridamole-induced flow deficit was underestimated by teboroxime when the rest study was performed first. Our results show that despite rapid myocardial clearance, tomographic imaging of 99mTc-teboroxime provides reasonably accurate quantitation of dipyridamole-induced anterior wall perfusion defects, but that the flow deficit is underestimated when a rest study is performed first or when the defect is located in the inferior wall.

Wiener filtering improves quantification of regional myocardial perfusion with thallium-201 SPECT.

Quantitation of myocardial perfusion with thallium-201 (201Tl) SPECT is limited by finite resolution and image noise. This study examined whether Wiener filtering could improve quantitation of the severity of myocardial perfusion deficits. In 19 anesthetized dogs, adjustable stenoses were placed on the left anterior descending (LAD, n = 12) or circumflex (LCx, n = 7) arteries. Thallium-201 SPECT images were acquired during maximal coronary vasodilation with dipyridamole, and simultaneous measurements of myocardial blood flow were made with microspheres. The relationship between SPECT and microsphere flow deficits in the LAD region was significantly better (p less than 0.05) with Wiener filtering (Y = 0.90X + 0.03, r = 0.78) than with conventional Hanning filtering (Y = 0.66X + 0.34, r = 0.61). Similarly, in the LCx region the relationship between SPECT and microsphere perfusion deficits was better (p less than 0.01) with the Wiener filter (Y = 0.91X + 0.07, r = 0.66) than with the Hanning filter (Y = 0.36X + 0.50, r = 0.40). Wiener filtering improves quantitation of the severity of regional myocardial perfusion deficits, allowing better assessment of the functional significance of coronary artery stenoses.

Myocardial redistribution of technetium-99m-methoxyisobutyl isonitrile (SESTAMIBI).

To determine whether technetium-99m-hexakis-2-methoxyisobutyl isonitrile (SESTAMIBI) remains fixed in the myocardium following its initial uptake or undergoes time-related redistribution, anesthetized dogs underwent occlusion of the anterior descending coronary artery for 6 min, followed by 3-hr reperfusion. Technetium-99m-SESTAMIBI and thallium-201 (201Tl) were injected intravenously after 1 min occlusion and regional myocardial blood flow was measured with radioactive microspheres. Tomographic imaging of Tc-SESTAMIBI revealed a perfusion defect with slight but definite filling in over 2 hr. Quantitative analysis indicated a significant rise in the nadir and decrease in the width of the defect in circumferential profile curves. After 3-hr of reperfusion, Tc-SESTAMIBI activity in the previously ischemic area was always greater than the activity of microspheres injected during coronary occlusion (mean normalized values, 0.32 versus 0.11, p less than 0.0001). Our results indicate that following transient ischemia and reperfusion, Tc-SESTAMIBI clearly undergoes myocardial redistribution, although more slowly and less completely than 201Tl.

Improved diagnostic performance of exercise thallium-201 single photon emission computed tomography over planar imaging in the diagnosis of coronary artery disease: a receiver operating characteristic analysis.

Qualitative interpretation of tomographic and planar scintigrams, a five point rating scale and receiver operating characteristic analysis were utilized to compare single photon emission computed tomography and conventional planar imaging of myocardial thallium-201 uptake in the accuracy of the diagnosis of coronary artery disease and individual vessel involvement. One hundred twelve patients undergoing cardiac catheterization and 23 normal volunteers performed symptom-limited treadmill exercise, followed by stress and redistribution imaging by both tomographic and planar techniques, with the order determined randomly. Paired receiver operating characteristic curves revealed that single photon emission computed tomography was more accurate than planar imaging over the entire range of decision thresholds for the overall detection and exclusion of coronary artery disease and involvement of the left anterior descending and left circumflex coronary arteries. Tomography offered relatively greater advantages in male patients and in patients with milder forms of coronary artery disease, who had no prior myocardial infarction, only single vessel involvement or no lesion greater than or equal to 50 to 69%. Tomography did not appear to provide improved diagnosis in women or in detection of disease in the right coronary artery. Although overall detection of coronary artery disease was not improved in patients with prior myocardial infarction, tomography provided improved identification of normal and abnormal vascular regions, particularly of the left anterior descending and circumflex artery regions. These results indicate that single photon emission computed tomography provides improved diagnostic performance compared with planar imaging in many clinical subgroups, and suggest that it represents the diagnostic imaging procedure of choice in exercise thallium-201 perfusion studies.

Technetium-99m methoxyisobutyl isonitrile (RP30) for quantification of myocardial ischemia and reperfusion in dogs.

This study was done to determine whether [99mTc]methoxyisobutyl isonitrile (RP30), a nonredistributing myocardial perfusion agent, could be used to quantify regional myocardial blood flow distribution during ischemia and reperfusion, employing sequential injections of tracer, tomographic imaging, and appropriate image subtraction. Dogs underwent transient (6 min) coronary artery occlusion, followed by two paired injections of RP30 and radioactive microspheres combined with tomographic imaging, the first during coronary occlusion and the second after 60 min of reperfusion. To obtain a true image representative of reperfusion, the first set of images was corrected for 99mTc decay and subtracted from the second. During occlusion, tissue microsphere content and scintigraphic RP30 activity in the center of the ischemic region (both expressed as a fraction of the nonischemic region) were closely correlated, although RP30 consistently exceeded microsphere content (0.43 +/- 0.03 vs. 0.24 +/- 0.04, p less than 0.01). Direct tissue counting of RP30 confirmed its relative excess in ischemic myocardium. Reperfusion was successful in 7/8 dogs, with an increase in RP30 activity to 0.98 +/- 0.04 compared to 0.89 +/- 0.03 for microspheres (p = N.S.). In one dog with microsphere-documented persistent ischemia, the RP30 defect was still present after reflow. Our results indicate that because of the lack of myocardial clearance and redistribution, repeat injections of RP30 can be used to quantify serial changes in regional myocardial blood flow.

Correction for patient and organ movement in SPECT: application to exercise thallium-201 cardiac imaging.

We describe a technique for correction of artifacts in exercise 201Tl single photon emission computed tomography (SPECT) images arising from abrupt or gradual translational movement of the heart during acquisition. The procedure involves the tracking of the "center of the heart" in serial projection images using an algorithm which we call "diverging squares". Each projection image is then realigned in the x-y plane so that the heart center conforms to the projected position of a fixed point in space. The shifted projections are reconstructed using the normal filtered backprojection algorithm. In validation studies, the motion correction procedure successfully eliminated movement artifacts in a heart phantom. Image quality was also improved in over one-half of 36 exercise thallium patient studies. The corrected images had smoother and more continuous left ventricular walls, greater clarity of the left ventricular cavity, and reduced streak artifacts. Rest injected or redistribution images, however, were often made worse, due to reduced heart to liver activity ratios and poor tracking of the heart center. Analysis of curves of heart position versus projection angle suggests that translation of the heart is common during imaging after exercise, and results from both abrupt patient movements, and a gradual upward shift of the heart. Our motion correction technique appears to represent a promising new approach for elimination of movement artifacts and enhancement of resolution in exercise 201Tl cardiac SPECT images.