Diagnostic spirometry in COPD is increasing, a comparison of two Swedish cohorts

Spirometry should be used to confirm a diagnosis of chronic obstructive pulmonary disease (COPD). This test is not always performed, leading to possible misdiagnosis. We investigated whether the proportion of patients with diagnostic spirometry has increased over time as well as factors associated with omitted or incorrectly interpreted spirometry. Data from medical reviews and a questionnaire from primary and secondary care patients with a doctors’ diagnosis of COPD between 2004 and 2010 were collected. Data were compared with a COPD cohort diagnosed between 2000 and 2003. Among 703 patients with a first diagnosis of COPD between 2004 and 2010, 88% had a diagnostic spirometry, compared with 59% (p < 0.001) in the previous cohort. Factors associated with not having diagnostic spirometry were current smoking (OR 2.21; 95% CI 1.36–3.60), low educational level (OR 1.81; 1.09–3.02) and management in primary care (OR 2.28; 1.02–5.14). The correct interpretation of spirometry results increased (75% vs 82%; p = 0.010). Among patients with a repeated spirometry, 94% had a persistent FEV1/FVC or FEV1/VC ratio <0.70.


INTRODUCTION
Chronic obstructive pulmonary disease (COPD) should be considered in patients who present with respiratory symptoms such as dyspnoea, cough, sputum production and a history of risk factors, especially smoking 1,2 .Spirometry is required to confirm a chronic obstruction and to confirm the diagnosis, using the ratio of the post-bronchodilator forced expiratory volume in one second (FEV 1 ) and the forced vital capacity (FVC) to less than 0.70 1,3 .However, several studies from various countries show a substantial underuse of spirometry in the initial assessment of patients with suspected COPD [2][3][4][5][6][7] .Both over-and underdiagnosis of COPD may thus occur, leading to suboptimal COPD care [8][9][10] .In Sweden, COPD is mainly diagnosed and managed in primary care 11 , where access to spirometers has increased during the last decades 12 .
In 2005, the first Swedish PRAXIS study COPD cohort with patients from both primary and secondary care was created (PRAXIS I).In this cohort, 59% of patients had a spirometry performed at diagnosis of COPD 13 .
In 2014, a new cohort of COPD patients (PRAXIS II) was recruited from the same geographic area.During the study period, the Swedish Board of Health and Welfare and the Swedish Medical Agency published guidelines for the diagnosis and management of patients with COPD based on the Global initiative for chronic Obstructive Lung Disease (GOLD) recommendations [14][15][16] .
The primary aim of this study was to investigate whether the proportion of performed spirometries at COPD diagnosis increased after the new national guidelines were implemented, and to investigate patient-related factors associated with a COPD diagnosis without a diagnostic spirometry.Secondary aims were to assess whether spirometries were correctly interpreted regarding COPD diagnosis, defined as airway obstruction FEV 1 /FVC < 0.70, and whether the obstruction was persistent at follow-up.
Patients without a diagnostic spirometry were significantly more often from primary care sites, had a lower educational level and were more often current smokers than those with a diagnostic spirometry (Table 1).These associations remained in the multivariate logistic regression (Table 2).
Patients with a registered COPD diagnosis yet an FEV 1 /FVC ratio ≥0.70, i.e. by definition an "incorrectly interpreted spirometry", were independently more often women, had hypertension, diabetes, milder COPD or a change of diagnosis from COPD to asthma during the study period when compared with those with an FEV 1 /FVC ratio <0.70 (Table 3).

Comparison of the two cohorts
The proportion of diagnostic spirometries increased from 59% to 88% (p < 0.001) when comparing the two cohorts, PRAXIS I and PRAXIS II (Fig. 1).

DISCUSSION
The primary finding of our study was that in patients with a doctors' diagnosis of COPD, spirometry performed within six months of diagnosis increased from 59% in the first PRAXIS cohort of 2000-2003 to 88% in the second PRAXIS cohort of 2004-2010.Factors associated with having a COPD diagnosis without a diagnostic spirometry were current smoking, low educational level and being managed in primary care.Secondary findings were that the FEV 1 /FVC or FEV 1 /VC ratios were incorrectly interpreted regarding COPD diagnosis in 18% of the cases.This finding was more likely in females, patients with concomitant hypertension or diabetes and those who were managed in primary care.In 94% of the patients with a correct COPD diagnosis, and where a follow-up spirometry was available in the records, airway obstruction was persistent over time.
Previously reported results from the first PRAXIS cohort 14 are consistent with other studies reporting that diagnostic spirometry was performed in about half to two-thirds of patients with a COPD diagnosis 4,5 .However, the present study from the second PRAXIS cohort shows that the frequency of performed diagnostic spirometries has clearly increased over time.There was also an increase in the proportion of correctly interpreted spirometries.We find it encouraging that the management of COPD in Sweden has improved and now complies with international and national diagnostic guidelines to a higher degree.The most important independent factor associated with not having performed a diagnostic spirometry was current smoking.We speculate that the clinical diagnosis of COPD in current smokers with respiratory symptoms may seem more obvious to physicians and thus explain the lower degree of confirmation with spirometry.Our finding is in line with a qualitative study by Joo et al. that presented a similar explanation of physicians´motives towards diagnosis of COPD 17 .Feng et al. conclude that people with multiple unhealthy lifestyles, including smoking, are less prone to consult primary health care 18 .Consequently, they would therefore not be referred to secondary care.This could explain the difference in primary and secondary care concerning the proportion of patients that did not undergo a diagnostic spirometry.
Smoking, poverty and low education are important factors associated with a higher burden of disease 19 .This is in line with our result of low education being associated with not having  performed a spirometry.Low socioeconomic status can be a reason why patients refrain from seeking care 20 .In Sweden, however, healthcare is financed with taxes and is equally available for everyone, thus the financial cost of healthcare cannot explain the lower frequency of spirometry testing in patients with low education.We speculate that our results could in part be due to a different care-seeking behaviour.For instance, smoking is found to be associated with reduced likelihood of care-seeking 21 .This highlights the importance of using a holistic approach and being aware of health inequalities when managing potential COPD patients, in order for individualised care and effective smoking cessation to be delivered.We believe that this result follows a pattern evident in other studies that have demonstrated associations between higher education and a higher degree of adherence to smoking cessation interventions and greater interest in learning self-management skills 22,23 .
The proportion of spirometries not consistent with a correct diagnosis of COPD was 18%.Similar misdiagnosis of COPD has been described previously, yet to a larger extent than in our study population 7,24 .In this particular group, we found a significant change of diagnosis from COPD to asthma over the study period (OR 9.90, 95% CI 3.09-31.78),indicating that these patients may have had asthma and not COPD from the beginning.Distinguishing asthma from COPD may be difficult, as untreated asthma may also have a temporary or persistent airway obstruction.The complexity of this differentiation was recently shown in a large global study 25 .We thus believe that some of the patients with a COPD diagnosis in our study may have had a suboptimally treated asthma where the diagnosis was changed from COPD to asthma after treatment and follow-up.Patients could also have had both asthma and COPD.A post hoc analysis showed 8.8% of patients with FEV 1 /FVC ≥ 0.70 had both a diagnosis of asthma and COPD recorded.In the group with FEV 1 /FVC < 0.70 the corresponding number was 9.6%, a non-significant difference.Another potential explanation of a COPD diagnosis in spite of a normal ratio is presence of "preserved ratio impaired spirometry" (PRISm), which can increase the risk of COPD, as well as nonpulmonary conditions in the future 26 .In a post hoc analysis, some 60% (n = 61) of the patients with an incorrect COPD diagnosis actually had PRISm.This may have contributed to a clinical diagnosis of COPD.Of these, 43 patients had overweight or obesity where the restrictive impairment of high BMI could have masked obstruction 26 .Furthermore, 6% of the patients did not have a persistent airflow obstruction when the first spirometries were compared to later ones.This may indicate an initial misdiagnosis, as these patients could have had asthma instead.This finding is consistent with a large UK study in which patients with an established COPD diagnosis did not have persistent airflow obstruction in 11.5% of cases 27 .Aaron et al. conclude that a single spirometric assessment may not be reliable for diagnosing patients with COPD, especially in patients with spirometry results close to the FEV 1 /FVC threshold 28 .An important clinical implication of our and others´findings is that spirometry should be repeated after treatment has been initiated in cases of newly diagnosed COPD.
A COPD diagnosis despite an FEV 1 /FVC or FEV 1 /VC ≥ 0.70 was more common in patients who had concomitant hypertension and diabetes.We speculate that this may indicate that the focus of the consultation was on these conditions rather than COPD.On the other hand, a post hoc analysis adding a merged index of all comorbid conditions listed in Table 1 to the multivariable model did not change the results significantly (data not shown).
We find it reasonable that the number of performed spirometries and the proportion of correct interpretations is higher in specialised pulmonology care than in primary care, and that the identification of airway obstruction is easier when COPD is more severe.
We believe the increase in the proportions of performed and correctly interpreted spirometries over time is a result of an extensive national educational effort to update and implement recommendations on the assessment of COPD.Furthermore, access to spirometers in primary care in Sweden is high.At the sites of our PRAXIS II cohort, 98% of the participating healthcare units reported that they had access to spirometers.Although the proportion of performed spirometries has increased, there is still room for improvement.In Denmark, general practitioners who participated in an educational programme showed substantial improvement in the assessment of patients with COPD 29 .This is in conformity with Sandelowsky et al. who concluded that educational interventions enhanced knowledge of COPD management in primary care in Sweden 30 .In Finland, a national programme for COPD prevention and treatment had significant positive consequences, including an increase in the use of spirometry 31,32 .Since most patients with COPD are diagnosed and managed in primary care, we believe continuous education addressed to primary care physicians is of great importance.A finding related to the interpretation of spirometries was that female sex was significantly associated with a COPD diagnosis despite a ratio ≥0.70.The reason for this is unclear.A potential explanation could have been that FEV 1 /FVC or FEV 1 /VC were closer to 0.70 for women.However, a post hoc analysis showed that ratios did not differ significantly between sexes (data not shown).Our result is in contradiction to a Spanish study where women were found not to have a COPD diagnosis despite fulfilled spirometric COPD criteria 33 .We speculate that, as symptoms of other diseases can have different clinical manifestations in women than in men 34,35 , the higher degree of spirometries with a ratio ≥ 0.70 in women with a diagnosis of COPD may mirror a more difficult differential diagnostic situation.
A major strength of our study is that it is a real-world study with a large sample size.This contributes to a high external validity and generalisability.Another strength is that, to the best of our knowledge, there are few studies with a follow-up of diagnostic assessment in two different cohorts from the same geographic area 28 .Limitations include the changes in national recommendations using FEV 1 /FVC instead of FEV 1 /maximum VC to confirm the diagnosis of COPD during the study period and that post-bronchodilator values were not present in all patients.Further, spirometry data was not always interpretable, which means a loss of patient data.However, the number of non-assessable spirometries was very low, and an attrition analysis showed that patients included in the analysis of spirometry interpretation and those who were excluded due to non-assessable spirometry data did not differ between any of the variables presented in Table 1 (data not shown).When completing a questionnaire there could be a risk of recall bias.
The second PRAXIS cohort included more primary health care centres (PHCCs) than the first PRAXIS cohort.However, a random selection was performed in both cohorts.Additional analysis where the extra PHCCs were excluded showed substantially unchanged results (data not shown).
The use of spirometry to confirm COPD diagnosis has increased over time, indicating improved implementation of COPD guidelines.At risk of not undergoing a diagnostic spirometry were current smokers, patients with low education and those managed in primary care.There is still a need for continuous medical educational activities to increase diagnostic accuracy.In the present study, patients were sampled from PRAXIS II.Patients were enrolled from the central hospitals, seven randomly selected district hospitals and 76 randomly selected PHCCs in seven regions in central Sweden.At each centre, all patients aged 18-75 years with a doctor's diagnosis of COPD (ICD-10 code J44) in their medical records during the period 2007-2010 were listed.An internet-based random selection (random.org) was performed from each site, resulting in a study basis of 2310 patients.In 2014 a letter of consent together with a questionnaire was sent to a total of 2310 patients, of which 1704 (74%) agreed to participate and returned the completed questionnaire.A review of the medical records was performed.This identified the present study population of 703 patients, 584 (83%) from primary and 119 (17%) from secondary care, who had received a diagnosis of COPD for the first time between 2004 and 2010 (Fig. 3).Previously published spirometry data from PRAXIS I was used to enable a comparison over time 14 .

Data collection and variables in the study
The questionnaire included sociodemographic data and information on health status including: • Age categorised as <65, 65-69 and ≥70 years.For the main analysis, age at the time of returning the questionnaire was used.For the presentation of spirometry staging according to GOLD, age at performed spirometry was used.
• Educational level: low educational level defined as <2 years beyond the nine years of Swedish compulsory school, and high educational level as ≥2 years beyond compulsory school.
• Smoking status categorised as current daily smoking or not.
• Exacerbations defined as a deterioration of the disease that required a course of antibiotics and/or oral steroids and/or an emergency visit and were presented as 0, 1, 2 and >2 during the previous 12 months.
• Health status assessed by the Swedish version of the COPD Assessment Test (CAT) 12 .The CAT scores were categorised into low, medium and high ( < 10, 10-19 and ≥20, respectively), according to GOLD 3 .Data on spirometry and comorbid conditions were retrieved by review of medical records for the period 2004-2014.Comorbidities were retrieved by diagnostic codes.Diabetes was defined as a diagnosis of types 1 or 2 diabetes mellitus and depression as a recorded diagnosis with or without concomitant antidepressant drug treatment.

Spirometry
Diagnostic spirometry was defined as a spirometry performed during the interval starting six months prior to diagnosis of COPD and ending six months after the first date of diagnosis.Spirometry data were available either as a separate spirometry report or as a part of the medical record.
For assessment of whether the interpretation of the diagnostic spirometry was correct, data on all available pre-and postbronchodilator values and ratios from FEV 1 , FVC and VC were collected.A ratio of FEV 1 /FVC or FEV 1 /VC < 0.70 was considered a "correctly interpreted spirometry" and a ratio of FEV 1 /FVC or FEV 1 /VC ≥ 0.70 was considered as an "incorrectly interpreted spirometry".
According to current guidelines, a post-bronchodilator FVC should be performed at diagnostic spirometries 1 .Earlier guidelines in Sweden recommended a post-bronchodilator VC.Depending on which data was available we chose to use either FEV 1 /FVC or FEV 1 / VC to assess whether the COPD diagnosis was correct.If both preand post-bronchodilator values were available, only postbronchodilator values were used.If both FEV 1 /FVC and FEV 1 /VC ratios were available, the lowest ratio was used in the evaluation.In addition, FEV 1 %pred was calculated according to the Global Lung Function Initiative (GLI) 36 in patients having undergone diagnostic spirometry.These FEV 1 %pred values were used to categorise patients in COPD stages 1-4 according to GOLD 1 .
When available, the most recent spirometry during the study period was also retrieved in the same manner as the diagnostic spirometry, in order to assess whether the airway obstruction was persistent over time.

Statistics
All statistical analyses were performed using IBM SPSS Statistics version 25 (IBM Corporation, Armonk, NY, USA).Descriptive analyses of the baseline study population characteristics were performed using cross-tabulation and the chi-square test.The proportion of performed spirometries, the proportion of spirometries with non-assessable data and the proportion of spirometries with FEV 1 /FVC or FEV 1 /VC ratios over and under 0.70 were calculated and presented as a circle diagram.For comparison, the same procedure was performed on the data from the previous cohort, PRAXIS I, where data was collected between 2000 and 2003.The proportions of performed spirometries and correctly interpreted spirometries were compared between the two cohorts using cross-tabulations and the chi-square test.
Logistic regression was used to analyse associations with nonspirometry verified diagnosis as well as incorrect spirometric diagnosis and several patient-related factors providing odds ratios (OR) for the independent variables.Univariate logistic regression used non-spirometry verified diagnosis of COPD as the dependent variable and patient characteristics as independent variables.In multivariate logistic regression, sex, age and factors with a statistically significant association in the univariate analysis were included.For studying associations with having a diagnosis of COPD in spite of an FEV 1 /FVC or FEV 1 /VC ≥ 0.70, univariate logistic regression was performed in patients with assessable spirometry data, using the same independent variables as in Table 1, with the addition of "change of diagnosis to asthma during the study period".Multivariate logistic regression was then performed with factors that were statistically significant in the univariate analysis.P values < 0.05 were considered statistically significant.

Fig. 1
Fig. 1 Diagnostic spirometry in patients with a new diagnosis of COPD.Comparison of COPD cohorts PRAXIS I, patients diagnosed in the period 2000-2003 (below) and PRAXIS II, patients diagnosed in the period 2004-2010 (above).

Fig. 2
Fig. 2 Proportion of patients with spirometry result FEV 1 /FVC or FEV 1 /VC above/equal to or under 0.70.Patients with assessable spirometry data and performed diagnostic spirometries from COPD cohorts PRAXIS I (n = 295) and PRAXIS II (n = 567).

Table 1 .
Patient characteristics distributed over performed and not performed diagnostic spirometry.

Table 2 .
FactorsMultivariate logistic regression with the factor "no diagnostic spirometry" as dependent variable.Adjusted for age, sex and patient characteristics significant in univariate logistic regression.OR Odds Ratio.

Table 3 .
Factors associated with an FEV 1 /FVC or FEV 1 /VC ratio ≥ 0.70, n = 102.with the ratio of FEV 1 /FVC or FEV 1 /VC ≥ 0.70 as dependent variable.Adjusted for age, sex and patient characteristics significant in univariate logistic regression.FEV 1 forced expiratory volume in 1 second, FVC forced vital capacity, FEV 1 %pred forced expiratory volume in 1 second as percentage of predicted value, OR Odds Ratio.Missing data: a Lung function categories, n = 35.