A Systematic Review on the Association between Schizophrenia and Bipolar Disorder with Chronic Obstructive Pulmonary Disease

Figures & data

Figure 1. Flow diagram study selection.

Table 1. Main characteristics of the studies evaluating chronic obstructive pulmonary disease in patients with schizophrenia or bipolar disorder.

Author/Year	Study design	Country^a	Data source	Time frame LOFU	Setting	Exposure definition^b			Outcome definition^b
						Schizophrenia	Bipolar disorder	Control
Bendayan 2022 [19]	CS	UK	A case register platform from the South London and Maudsley National Health Service Foundation Trust (UK)	2007-2018 NA	Out	ICD-10	ICD-10	No	Mapping with MedCaT, a natural language processing tool
Brink 2019 [21]	RC^c NRB	Denmark	National Danish Registries	1970-1979 10 years	In & Out	Patients admitted to a psychiatry hospital with ICD-8 Dx	–	General population (without schizophrenia)	ICD-8 and ICD-10 codes
Carney 2006 [27]	CS PB^d	US	Wellmark Blue Cross/Blue Shield of Iowa (USA) administrative claims database	1996-2001 NA	In & Out	Schizophrenia or schizoaffective disorder (ICD-9)	–	General population (without mental disorder)	Elixhauser Comorbidity Index
Carney 2006 [32]	CS PB^b	US	Wellmark Blue Cross/Blue Shield of Iowa (USA) administrative claims database	1996-2001 NA	In & Out	–	ICD-9	General population (without mental disorder)	Elixhauser Comorbidity Index
Copeland 2007 [28]	CS NRB	US	Patients discharged at death from Veterans Administration hospitals (USA)	October 1, 2001-September 30, 2002 NA	Unclear	Diagnosis of schizophrenia (ICD-9) in the past year	–	Without schizophrenia	Diagnosis of COPD (ICD-9) during the last year of life (or during the last hospitalization)
Crump 2013 [22]	RC NRB	Sweden	Swedish national linked registries	2003-2009 7 years	In & Out	ICD-10	–	General population (without schizophrenia)	ICD-10
Crump 2013 [26]	RC	Sweden	Swedish national linked registries	2003-2009 7 years	In & Out	-	ICD-10	General population (without bipolar disorder)	ICD-10
Hendrie 2014 [35]	CS & RC	US	Wishard Health Services. Health provider to the uninsured or underinsured (Indianapolis, US). Patients who reached 65 years within the study time frame period	1999-2008 Mean: 5.7 years (cases) and 6.7 years (controls)	Out	ICD-9	–	Patients without schizophrenia	ICD-9
Hetlevik 2015 [29]	CS NRB	Norway	The Regular GP database, a national Norwegian database of general practitioners claims data	2009 NA	Out	International Classificaction of Primary Care (ICPC) code	No	General population	Diagnosis of obstructive lung disease (ICPC)
Hsu 2013 [23]	CS & RC PB^b	Taiwan	National Health Research Institute (NHRI) medical claims database (Taiwan)	2005-2008 4 years	In & Out	ICD-9	No	General population	ICD-9
Hsu 2017 [25]	CS & RC PB^b	Taiwan	National Health Research Institute (NHRI) medical claims database (Taiwan)	2005-2010 6 years	In & Out	No	ICD-9	General population	ICD-9
Khaykin 2010 [30]	CS NRB	US	Nationwide Inpatient Sample (NIS) study of United States hospital discharges for adults 18 years and older	2002-2007 NA	Inpatient (nonpsychiatric hospitalizations)	ICD-9	–	Hospital controls (hospitalizations without schizophrenia)	AHRQ’s clinical classification software
Kilbourne 2004 [34]	CS PB^b	US	National Patient Care Database of the Veterans Health Administration (US)	2001 NA	In & Out	–	ICD-9	General Veterans Administration patient population	ICD-9
Krieger 2019 [24]	RC NRB	Israel	Nationwide data, derived from the Clalit Health Services (CHS) databases, the largest public managed health care organization in Israel	2017 NR	Out	ICD 9-10 (smoking)	–	Healthy smoking controls	ICD-9
Partti 2015 [18]	CS PB^b	Finland	The Health 2000 Survey, a nationwide health examination study conducted in Finland	September 2000, June 2001	Out	DSM-IV-TR based on health survey questionnaire and medical records	Affective psychosis, including BD (DSM-IV-TR)	General population (without psychosis)	Hospital admission because of COPD or diagnosis by spirometry
Perugi 2015 [36]	CS	Italy	Units of the Department of Psychiatry at the University of Pisa	NR	In & Out	–	DSM-IV (SCID-I)	No	Diagnosis by a physician
Schoepf 2014 [31]	CS & RC	UK	General Manchester NHS Hospitals	January 1, 2000-June 30, 2012 12.5 years	Inpatient	ICD-10 admitted to a general hospiatal	No	Hospital controls	Diagnosis at discharge
Schoepf 2014 [37]	CS & RC	UK	General Manchester NHS Hospitals (UK)	January 1, 2000-June 30, 2012 12 years	Inpatient	No	ICD-10 admitted to a general hospital	Hospital controls	Diagnosis at discharge
Sokal 2004 [20]	CS	USA	Psychiatric care facilities at two centers in Maryland (US)	2000	Out	Unclear shizophrenia and schizaffective disorder	Unclear affective disorder	Historical controls from the US National Health Interview Survey and the National Health and Nutrition Examination Survey	Diagnosis of comorbidities using the NHIS and NHANES questionnaire, including chronic bronchitis and emphysema

^aCountry where the study was conducted; ^bWhen only appears, the coding system means that diagnosis was based on the existence of the corresponding code; ^cAlthough described by the authors as a nested case–control study, we think it could be considered a retrospective cohort study evaluating the relationship between an exposure (i.e. having or not having a diagnosis of schizophrenia) and several outcomes including incident cases of COPD; ^dAs categorized by the authors.

CS, cross-sectional study; ICD, International Classification of Diseases; In, inpatients; IPCP, International Classification of Primary Care coding system; LOFU, length of follow-up; NA, not applicable; NR, not reported; NRB, national register-based; Out, outpatients; PB, population-based; RC, retrospective cohort study.

Table 2. Longitudinal studies evaluating the association between schizophrenia and the occurrence of COPD.

Author/Year	Study group	Sample size	Age (year)	Sex (% female)	Smoking status		Association
					Measure	%	Effect measure Covariates	Point estimate (95% CI)	p value
Brink 2018 [21]	Schizophrenia	4.544	34,3	33,6	NR	NR	RR Age, sex, calendar year	30-39 years: 1.43 40-49 years: 1.06 50-59 years: 1.53* 60-69 years: 1.70* 70-79 years: 1.98*	*Statistically significant
	Control	22.597	33,9	32,1	NR	NR
Crump 2013 [22]	Schizophrenia	8277	NR	42.2	Reported smoking prevalences	70	HR A. Age and other sociodemographics B. Plus substance use disorder	Women/Men A. 2.58 (2.26-2.94)/ 2.12 (1.84-2,45) B. 2.06 (1.80-2.34)/ 1.53 (1.32-1.76)	NR
	Control	6097834	NR	51.3	Reported smoking prevalences	25
Hsu 2013 [23]	Schizophrenia	4417	NR	NR	NR	NR	RR Age, sex, insurance amount	1.83 (1.62-2.07)	<0.001
	Control	762010	NR	NR	NR	NR
Krieger 2019 [24]	Schizophrenia	10502	49.66	NR	Unclear (# cigarettes)	14.0	OR (for having a diagnosis of COPD after first documented smoking) Age, sex, socioeconomic status, marital status, obesity, diabetes, hypertension, CHF, cardiomyopathy, hyperlipidemia, alcohol abuse, drug abuse	2.53 (2.23-2.87)	<0.001
	Control (smokers)	10502	49.66	NR	Unclear (# cigarettes)	14.3

CI, confidence interval; HR, hazard ratio; NR, not reported; OR, odds ratio; RR, relative risk/rate ratio.

^aCrude estimation from the proportion of patients with COPD provided in the article.

Table 3. Longitudinal studies evaluating the association between bipolar disorder and the occurrence of COPD.

Author/Year	Study group	Sample size	Age (year)	Sex (% female)	Smoking status		Association
					Measure	%	Effect measure Covariates	Point estimate (95% CI)	p value
Crump 2013 [26]	Bipolar	6618	No	59.2	Reported smoking prevalences	70	HR A. Age and other sociodemographics B. Plus substance use disorders	Women/Men A. 2,86 (1.99-4.12)/ 2.57 (1.60-4.14) B. 2.09 (1.45-3.02)/ 2.03 (1.26-3.27)	No
	Control	6587036	No	51.1	Reported smoking prevalences	25
Hsu 2017 [25]	Bipolar	1848	No	No	No	No	RR Age, sex, insurance status, region, urbanicity	1.94 (1.65-2.29)	<0.001
	Control	764579	No	No	No	No	No	No	No

CI, confidence interval; HR, hazard ratio; RR, relative risk/rate ratio.

Table 4. Prevalence of chronic obstructive pulmonary disease in patients with schizophrenia in cross-sectional studies.

Author/Year	Study group	Sample size	Age, years (mean)	Sex (% female)	Smoking status		Prevalence (%)
					Measure	%
Bendayan 2022 [19]	Schizophrenia spectrum disorders	13019	NR	41.6	NR	NR	2.6
Carney 2006 [27]	Schizophrenia	1.074	40,2	53	Nicotine abuse/dependence conditions	8,8	10.8
Copeland 2007 [28]	Schizophrenia	943	69.7	3.3	Nicotine dependence (including prescription)	9.7	45.7
Hendrie 2014^a [35]	Schizophrenia	757	69.96	69.22	Ever smoked	56.7	52.71
Hetlevik 2015 [29]	Schizophrenia	10112	43	38.1	NR	NR	6.7
Hsu 2013 [23]	Schizophrenia	4417	NR	NR	NR	NR	3.83
Khaykin 2010 [30]	Schizophrenia	269387	56.2	51.9	NR	NR	26.6
Partti 2015 [18]	Schizophrenia	67	53.4	56.7	Smoking >1 pack per day	30.8	12.2
Schoepf 2014 [31]	Schizophrenia	1418	49.8	39.4	NR	NR	8.1
Sokal 2004 [20]	Schizophrenia	92	42.4	37	Ever smoked	79.0	Chronic bronchitis: 15.2 Emphysema: 9.8

NR, not reported.

^aThe design of this study is unclear. However, it seems that it provided cross-sectional data for comorbidities and longitudinal results for mortality; thus, when describing characteristics of patients and presenting the frequency of comorbidities, the authors used the term “prevalence”.

Table 5. Prevalence of chronic obstructive pulmonary disease in patients with bipolar/affective psychosis in cross-sectional studies.

Author/Year	Study group	Sample size	Age (year)	Sex (% female)	Smoking status		Prevalence (%)
					Measure	%
Bendayan 2022 [19]	Bipolar disorder	4481	NR	60.3	NR	NR	3.0
Carney 2006 [32]	Bipolar disorder	3557	39.3	60.8	Nicotine abuse/dependence conditions	9.1	12.9
Hsu 2017 [25]	Bipolar disorder	1848	NR	NR	NR	NR	5.68
Kilbourne 2004 [34]	Bipolar disorder	4310	53	10	NR	NR	10.6
Partti 2015 [18]	Affective psychosis^a	49	53.9	46.9	Smoking >1 pack per day	18.0	12.4
Perugi 2015 [36]	Bipolar disorder	347	47.7	62.8	NR	NR	5.5
Schoepf 2014 [37]	Bipolar disorder	621	47.3	58.9	NR	NR	7.6

NR, not reported.

^a It included major depressive disorder with psychotic features and bipolar I disorder.

Table 6. Factors associated with the presence or occurrence of COPD in patients with schizophrenia or bipolar disorder.

Author/Year	Study design	Exposure	Matching	Multivariate analysis and covariates	Results
Hsu 2013 [23]	Population-based CS & RC	Schizophrenia vs. General population	Age, sex, insurance amount	Cox regression: age, sex, insurance amount, region, urbanicity, antipsychotic use	Longitudinal analysis: HR Age (18–29): 30–39: 1.21 (0.78–1.89); 40–49: 1.54 (1.01–2.36); 50–59: 2.65 (1.72–4.07); 60–69: 2.85 (1.67–4.86); 70 or over: 3.61 (1.97–6.62) Sex (Female): Male: 1.37 (1.07–1.76) The remaining factors were not significantly associated
Hsu 2017 [25]	Population-based CS & RC	Bipolar disorder vs. General population	Age, sex, insurance amount, region and urbanicity	Logistic regression & Cox regression analyses: age, sex, insurance amount, region and urbanicity, antipsychotic use, antidepressant use, mood stabilizer use, diabetes, hypertension, and hyperlipidemia	Cross-sectional analysis: OR Age (18–29): 30–39: 1.73 (0.69–4.35); 40–49: 2.55 (1.09–5.98); 50–59: 2.78 (1.14–6.75); 60–69: 2.89 (1.13–7.39); 70 or over: 7.16 (2.90–17.67) Sex (female): Male: 1.68 (1.10–2.58). Antidepressant use (none): first generation: 0.28 (0.04–2.18); second generation 1.92 (1.23–2.99) Hypertension (No): 2.11 (1.30–3.43) The remaining factors were not significantly associated with the presence of COPD Longitudinal analysis: HR Age (18–29): 30–39: 2.12 (1.10–4.11); 40–49: 3.12 (1.66–5.84); 50–59: 3.51 (1.81–6.82); 60–69: 3.00 (1.39–6.51); 70 or over: 9.39 (4.32–20.40). The remaining factors were not significantly associated with the occurrence of COPD
Kilbourne 2004 [34]	CS	Bipolar disorder vs. General population	No	Logistic regression (race, age, sex, copayment status and marital status)	African–American: 0.58 (0.39–0.84) Age 60 or over: OR 3.04 (2.47–3.74) Female: 1.03 (0.73–1.46) No copayment: 1.75 (1.14–2.67) Not married: 1.24 (1.00–1.54)^a

CS, cross-sectional study; RC, retrospective cohort study.

The authors stated that “Patients not requiring a copayment (“no copayment”) are considered lower income, and hence, this variable is a proxy for socioeconomic status”.

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Data availability statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.