2. ERUPCION DENTAL
2.4 FASES DE LA ERUPCION DENTAL
Summary
• This study aims to quantify how commonly patients with COPD have a concomitant diagnosis of asthma, and how commonly patients with asthma have a concomitant diagnosis of COPD in UK primary care.
• 400 COPD patients and 351 asthma patients were identified from the Clinical Practice Research Datalink (CPRD) GOLD in separate validation studies and the diseases were confirmed by the review of GP questionnaires by two study physicians.
• We examined the prevalence of concurrent asthma and COPD based on CPRD GOLD coding, GP questionnaires and requested additional information. We also aimed to determine the extent of possible misdiagnosis and missed opportunities for diagnosis.
• A concurrent asthma and COPD diagnosis appears to affect a relative minority of patients with COPD (14.5%, 95% CI 11.2-18.3) or asthma (14.8%, 95% CI 11.3- 19.0).
• More than half of the validated COPD patients had ever received an asthma diagnosis Read code, suggesting over diagnosis of asthma in COPD patients commonly occurs, particularly early in the diagnostic process.
• Over diagnosis of COPD in asthma patients and under diagnosis of asthma or COPD in patients with the other disease are less likely.
143
5.1 Preface
The study included in this chapter quantifies and discusses concomitant diagnosis of asthma and COPD in the CPRD GOLD. In brief, we aimed to quantify the point prevalence of concomitant asthma and COPD in the diagnosed populations of both asthma and COPD patients in the UK using the CPRD GOLD. Validated definitions exist for the identification of both diseases in the CPRD GOLD. In addition, we also examined possible misdiagnosis and missed diagnosis in patients with obstructive lung diseases.
The distinction between the two diseases in electronic health records is not trivial, as they share many symptoms and characteristics. In addition, there was a gap in the current literature on the prevalence of concomitant disease in primary care.
The concomitant diagnosis of asthma and COPD has been grounds for controversy within respiratory medicine research. The existence of both diseases in the same patient has been accepted, but the mechanism of the underlying pathology has been cause for discussion. The Dutch hypothesis suggests that both diseases are manifestations of the same disease process, with asthma preceding COPD. The overlap syndrome is then called “Asthma COPD Overlap Syndrome” (ACOS). The other school of thought, sometimes called the British hypothesis, proposes asthma and COPD are distinct disease entities with different causal mechanisms. Asthma and COPD can coexist independently in the same patient according to this hypothesis.(111)
The group of individuals with a concomitant diagnosis merits attention, as patients with both asthma and COPD have more frequent exacerbations, increased morbidity and mortality, faster lung function decline and a poorer quality of life than patients with only asthma or only COPD.(312,313)
144
Epidemiological studies on concomitant asthma and COPD have been scarce, as the differential diagnosis of both diseases is difficult (single spirometry measurements cannot clearly distinguish between asthma and COPD).(314,315) In addition, many studies have insisted on a separation of both diseases, excluding asthma patients from COPD studies and vice versa to avoid misclassification and these studies are also based on narrow inclusion criteria.(316,317) . The symptoms of asthma and COPD overlap, and the differential diagnosis is not always trivial to make. Information on reversibility testing, the QOF indicators, smoking status, concurrent respiratory diseases and other sources including consultant and hospital discharge letters, lung function tests and radiography results was requested in the questionnaire.
A review of this information by a respiratory consultant and study GP aimed to identify the actual cases of COPD in confirmed asthma patients. This review was used as the gold standard to calculate the PPV, NPV, sensitivity and specificity of recorded GP diagnoses of COPD in the primary care records of asthma patients.
The availability of the data of two validation studies provided the opportunity to look at the prevalence of COPD in validated asthma patients in the CPRD GOLD, and the prevalence of asthma in validated COPD patients in the CPRD GOLD. The data on the validated asthma patients came from the study included in the previous chapter, and the data on the validated COPD patients came from an earlier validation study of COPD recording in the CPRD by Quint JK et al, in which I did not participate.
The validation studies are available here:
• Nissen F, Morales DR, Mullerova H, Smeeth L, Douglas IJ, Quint JK. Validation of asthma recording in the Clinical Practice Research Datalink (CPRD). BMJ Open. 017;7(8). https://www.ncbi.nlm.nih.gov/pubmed/28801439
• Quint JK, Mullerova H, DiSantostefano RL, Forbes H, Eaton S, Hurst JR, et al. Validation of chronic obstructive pulmonary disease recording in the Clinical Practice
145
Research Datalink (CPRD-GOLD). BMJ Open. 2014;4(7):e005540. https://www.ncbi.nlm.nih.gov/pubmed/25056980
This paper was accepted for publication in the British Journal of General Practice.
• Francis Nissen, Daniel R.Morales, Hana Mullerova, Liam Smeeth, Ian J Douglas,
Jennifer K Quint ‘Quantifying concomitant diagnosis of asthma and COPD in UK primary care.’ BJGP 2018
146
5.2 Research paper
Quantifying concomitant diagnosis of asthma and COPD in UK primary care
Authors: Francis Nissen,1 Daniel R. Morales,2 Hana Mullerova,3 Liam Smeeth,1 Ian J Douglas,1 Jennifer K Quint4
1. Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
2. Division of Population Health Sciences, University of Dundee, Dundee, UK 3. RWE & Epidemiology, GSK R&D, Uxbridge, UK
4. National Heart and Lung Institute, Imperial College, London, UK
ABSTRACT
Background: Asthma and COPD share many characteristics and symptoms, and the differential diagnosis between the two diseases can be difficult in primary care. This study explores potential overlap between both diseases in a primary care environment.
Aim: This study aims to quantify how commonly patients with COPD have a concomitant diagnosis of asthma, and how commonly patients with asthma have a concomitant diagnosis of COPD in UK primary care.
Design and Setting: 400 COPD patients and 351 asthma patients were identified from the Clinical Practice Research Datalink (CPRD) in separate validation studies and the diseases were confirmed by review of GP questionnaires.
147
Method: The prevalence of concurrent asthma and COPD in validated cases of either disease was examined based on CPRD coding, GP questionnaires and requested additional information. We also aimed to determine the extent of possible misdiagnosis and missed opportunities for diagnosis.
Results: More than half (52.5%) of validated COPD patients had ever received a diagnostic asthma Read code. However, when considering additional evidence to support a diagnosis of asthma, concurrent asthma was only likely in 14.5% (95% CI: 11.2%; 18.3%) of validated COPD patients. Of the validated asthma patients, 15.1% have ever received a diagnostic COPD Read code, although COPD was only likely in 14.8% (95% CI: 11.3%; 19.0%) of validated asthma patients.
Conclusion: A concurrent asthma and COPD diagnosis appears to affect a relative minority of patients with COPD (14.5%) or asthma (14.8%). Asthma diagnosis may be over recorded in people with COPD.
How this fits in
The prevalence of concomitant asthma and COPD is likely to be overestimated in studies using only electronic health records as their symptoms are similar. This study reports on this issue by including only validated asthma and COPD patients from two previous validation studies. A concurrent asthma and COPD diagnosis affects a relative minority of patients in primary care with either asthma (14.8%) or COPD (14.5%). Asthma may be over recorded in people with COPD in electronic health records.
148
INTRODUCTION
Worldwide, 358 million people are estimated to be affected by asthma (299) and 174 million by COPD (Chronic Obstructive Pulmonary Disease).(41) Both diseases can vary greatly in their presentation and imprecision of diagnosis in both diseases remains a problem. (304,305)
Accurate diagnosis of asthma and COPD is essential, as correct treatment of asthma and COPD can reduce the frequency and severity of exacerbations and improve overall quality of life.(41) In addition, information on chronic respiratory disease can help patients to quit smoking.
The differential diagnosis of COPD and asthma rests on differences in clinical presentation, triggering factors, and on demonstration of reversibility of airflow obstruction. This airflow obstruction is not fully reversible in COPD, whereas it is in asthma. However, the differential diagnosis remains difficult and the existence of an overlap syndrome called ACOS (Asthma-COPD Overlap Syndrome) remains controversial,(318,319) as consensus regarding the clinical definition has not yet been reached. Some guidelines classify asthma cases with a persistent airway obstruction as COPD, and the two diseases are often mutually exclusive in studies to obtain unblended populations of asthma and COPD patients. In addition, the prevalence of a concomitant diagnosis of asthma and COPD varies greatly in different studies.
This study aims to quantify the point prevalence of concomitant asthma and COPD in the diagnosed populations of both asthma and COPD patients in the UK using electronic health record databases where validated definitions exist for the identification of both diseases. In addition, we also examine possible misdiagnosis and missed diagnosis in patients with obstructive lung diseases.
149
METHODS
Study population and validation studies
The study populations consist of people who were included in earlier validation studies.(297,320) and are summarised in figure 1 and 2. Questionnaires were sent out to the GPs of possible asthma and COPD patients with the intent to validate the recording of asthma and COPD in the CPRD. The full selection criteria of both validation studies can be found in their respective articles.(297,320) Patient data for the asthma recording validation study were collected from 1 December 2013 to 30 November 2015, and patient data for the COPD recording validation study was between 1 January 2004 and 31 December 2012. In the asthma validation study, full data was only available for the patients for whom the GP stated a current asthma diagnosis and only current asthma diagnoses were considered. In the COPD validation study, the population was preselected as current or ex-smokers. The two patients populations included in this study have been thoroughly validated in their respective validation studies using these detailed GP questionnaires and requested supporting information including outpatient referral letters, other emergency department discharge letters, airflow measurements and radiography records. In the validation studies, the Positive Predictive Value was 86.5% (77.5-92.3%) for COPD (297) and 86.4% (77.4%-95.4%) for asthma (320) when only using a single diagnostic code for the respective disease.
In the asthma questionnaire, details were requested on evidence of airway obstruction, current symptoms, smoking history, respiratory comorbidities and Quality Outcome Framework (QOF) indicators (QOF is a national financial incentive scheme for GPs in the UK encouraging regular disease indicator measurement and recording). The COPD questionnaire requested information on COPD diagnosis, smoking history, symptoms, spirometry, confirmation by a respiratory physician and respiratory comorbidities. Additional information available from the medical record including spirometry printouts and letters from respiratory physician or hospitals
150
were also requested. Data were encrypted twice to ensure anonymity. If a questionnaire was returned blank or every question was answered “unknown”, it was considered invalid.
Database
The Clinical Practice Research Datalink (CPRD) GOLD is a large anonymised UK primary care database which is representative of the UK population with regard to age and sex.(306) Diagnostic accuracy has been demonstrated to be high in CPRD GOLD for many conditions,(229) including asthma and COPD. This database contains detailed clinical information on diagnoses, prescriptions, laboratory tests, symptoms and hospital referrals of included individuals, in addition to basic sociodemographic information recorded by the general practitioners. In the original validation studies, lists of medical codes (Read codes) deemed as specific for asthma or COPD were used to select algorithms to identify asthma and COPD patients; these codes have a high validity in their respective validation studies. Read codes are a hierarchical clinical coding system that is used in general practices in the UK; each Read code is linked to a specific string of text, which refers to a single diagnosis or symptom.
Primary outcome and measurements
The primary outcome for this study was the proportion of patients with either asthma or COPD who had the other disease in the validated asthma and COPD populations. The presence of a diagnostic asthma Read code and positive reversibility tests supported an asthma diagnosis in the COPD population. The presence of a diagnostic COPD Read code, smoking history and fixed airflow obstruction supported a current COPD diagnosis in the population with validated asthma. Spirometry measurements with at least one airflow measurement with fev1/fvc ≤ 70% were considered as evidence for an obstructive airflow limitation. The quality of the spirometry procedure undertaken in UK primary care to diagnose COPD is high as determined in a previous validation study.(321)
151
Possible misdiagnosis and/or lacking diagnosis of asthma in validated COPD patients, and vice versa, were examined using spirometry measurements, results of reversibility tests and smoking history. To study the temporality of recorded diagnostic Read codes in patients with concomitantly recorded asthma and COPD, we reported the proportion of patients where the time lapse between the date of validation of one disease and the last known diagnosis of the other disease was greater than two years. This was done as we had learned from the validation studies that a COPD patient would sometimes receive their first asthma diagnosis in the 2 years leading up to the first COPD diagnosis. An asthma code shortly before a first diagnosis of COPD is likely to be a misdiagnosis of asthma. If the asthma code was given multiple years before the COPD diagnosis, asthma before COPD onset is more probable.
Conversely, if the last COPD code was given more than 2 years before the validation of an asthma diagnosis (and we assume the validated asthma diagnosis is true), the COPD might be misdiagnosed as the code was not repeated afterwards.
Asthma and COPD diagnoses are based on symptoms, signs and spirometry, but there is no clear reference test. A panel consisting of two physicians determined whether asthma or COPD were present in the validated patients using all available information, and according to national and international guidelines. Both physicians were blinded to the patient selection algorithm and adjudicated the asthma and COPD statuses independently. Where opinion differed, the cases were discussed, and agreement was reached by consensus.
Statistical analysis
We calculated the proportion of asthma patients with COPD and vice versa with 95% confidence intervals using exact binomial Clopper-Pearson intervals. Cells with less
152
than 5 entries were merged for presentation. All analyses were conducted using Stata 14.0 in 2017.
153
Table 1: Baseline characteristics
Data Source Asthma validation Total COPD validation Total
COPD Read code No COPD Read code Asthma Read code No Asthma Read code
Individuals (%) 52 (15%) 299 (85%) 351 210 (52%) 190 (48%) 400
Mean age: (95% CI) 67 (64-70) 45 (42- 47) 48 (46-50) 73 (71-74) 73 (72-75) 73 (72-74)
Sex: male (%) 22 (42%) 114 (38%) 136 (39%) 99 (47%) 104 (55%) 203 (51%)
(Ex-) smoker (%) 43 (82%) 112 (37%) 200 (57%) * * *
*The COPD population was preselected to only include (ex-) smokers
154
RESULTS
Background characteristics
The baseline characteristics of the 751 patients with confirmed asthma and COPD diagnoses are shown in table 1. Amongst patients with validated asthma, those with a COPD diagnosis were older than those without (67 and 45 years, respectively). There was no noticeable difference in mean age between validated COPD patients with or without an asthma Read code (73 years in both groups). The validated asthma study population was mostly female (61.2%), while the validated COPD population was more evenly split regarding sex (50.7% male). The table is further split into two age categories. In the validated asthma patients, a concomitant COPD diagnosis is more likely when the patient is over 50 years of age. Only a small percentage of validated COPD patients is under 50 years of age.
Validated asthma patients
We studied 351 patients with a validated asthma diagnosis of which 52 (15%) had a recorded COPD Read code. The details are summarised in figure 1. For 6 of the 52 asthma patients with COPD codes, the COPD codes were more than 2 years prior to asthma validation. For the remaining 46, COPD codes were within 2 years of the asthma validation date. Of the 46 with validated asthma and recent COPD codes, 38 were smokers or ex-smokers and 8 were recorded as never-smokers. Out of 299 asthma patients without COPD codes, 112 were (ex-) smokers, while 187 were recorded as never-smokers.
We assumed concomitant asthma and COPD in validated asthma patients in the following cases: if the validated asthma patients had a recent diagnosis of COPD and were (ex-) smokers; or if they showed obstruction on their spirometry and were (ex-) smokers but lacked a COPD code. As such, concomitant asthma and COPD was likely in 52 patients (14.8%, 95% CI: 11.3%-19.0%): 38 of those 52 patients had a recent COPD
155
diagnosis (within 2 years of their asthma Read code) and were smokers or ex-smokers; the remaining 14 patients had no COPD Read code but showed obstruction on their spirometry and were smokers or ex-smokers.
We assumed solitary asthma (without COPD) in validated asthma patients in three scenarios: either if they did not have a COPD code nor showed obstruction on lung function tests; or if they had a past COPD code more than two years ago (as the coding should have been repeated); or if they had a recent COPD code but no smoking history. As such, a solitary diagnosis of asthma was likely in 299 patients (85.2%; 95% CI 81.0-88.7): 187 never smokers without a COPD Read code, 98 (ex) smokers without obstruction or a COPD Read code, 8 patients with a recent COPD code but no smoking history, and 6 patients whose COPD Read code was more than 2 years since their last asthma code.
Validated COPD patients
We studied 400 patients with a validated COPD diagnosis, of which 210 (52%) had a recorded asthma Read code. The details are summarised in figure 2. For 82 of the 210 COPD patients with asthma codes, the asthma codes were more than 2 years prior to COPD validation. For the remaining 128, asthma codes were within 2 years of the COPD validation date. Of the 128 with validated COPD and recent asthma codes, 42 had a recording of positive reversibility testing and 86 did not have a recording of positive reversibility testing. Out of 190 COPD patients without asthma codes, 16 had a recording of positive reversibility testing, while 174 did not have lung function tests indicating reversibility of their airflow obstruction.
We assumed concomitant asthma and COPD in validated COPD patients in two scenarios: validated COPD patients with a recently recorded asthma code and a recording of positive reversibility testing; and validated COPD patients without a recent asthma code but with positive reversibility testing recorded. As such,
156
concomitant asthma and COPD was likely in 58 patients (14.5% (95% CI 11.2%- 18.3%)): 42 patients who had a recently recorded asthma diagnosis and positive reversibility testing recorded, in addition to 16 patients without asthma Read codes who had positive reversibility testing recorded.
We assumed solitary COPD (without asthma) in validated COPD patients based on the following criteria: validated COPD patients with no asthma codes nor recording of positive reversibility testing; validated COPD patients where the last asthma code was more than two years before asthma validation (indicating asthma prior to COPD);