Effectiveness of Influenza Vaccination for Individuals with Chronic Obstructive Pulmonary Disease (COPD) in Low- and Middle-Income Countries

Figures & data

Table 1. Studies included for review

	Authors	Year	Country	Study design (Sample size)	Outcome measure
1	Seo et al. (21)	2014	Korea	Case control (828)	Hospitalization
2	Montserrat-Capdevila et al. (22)	2014	Spain	Retrospective cohort (1323)
3	Kiyohara et al. (23)	2013	Japan	Cohort – secondary data January 1995–December 2009 (202 338 COPD deaths)	Mortality
4	Anar et al. (15)	2010	Turkey	Cross-sectional (82)	Antibody titres, seroconversion rates and seroprotection and Hospitalization
5	Chuaychoo et al. (11)	2010	Bangkok	Randomized Trial comparing vaccines (160)	Antibody titres, seroconversion rates and seroprotection
6	Schembri et al. (24)	2009	Tayside, Scotland	Cohort -Secondary data from The Health Improvement Network (THIN) database (77,120)	Mortality
7	Ayabe et al. (25)	2009	Japan	Cohort (289)	Pneumonia and acute exacerbations of CLD
8	Sumitani et al. (26)	2009	Japan	Retrospective cohort additive inoculation of influenza vaccine (IIV) and 23-valent pneumococcal vaccine (PV)	Hospitalization
9	Furumoto et al. (27)	2009	Japan	Trial comparing vaccine types (167)	Pneumonia and acute exacerbations of CLD
10	Menon et al. (14)	2008	India	Cohort (87 males)	Number of ARI classified as outpatient treatment, hospitalizations and need for mechanical ventilation
11	Wang et al. (16)	2007	Taiwan	Retrospective cohort (35,637)	Mortality
12	Karwat et al. (28)	2007	Poland	Cohort (178 asthma and COPD)	Pneumonia and acute exacerbations of CLD
13	Kositanont et al. (13)	2004	Thailand	RCT (123)	Laboratory diagnosed influenza caused illness (LDI)
14	Wongsurakiat et al. (12)	2004	Bangkok, Thailand	RCT comparing vaccine and placebo (125)	Number of ARI classified as outpatient treatment, hospitalizations and need for mechanical ventilation
15	Gorse et al. (29)	2003	US VA hospital	RCT comparing vaccine types (2215)	Laboratory diagnosed influenza caused illness (LDI)
16	Gorse et al. (30)	1997	US, VA hospital	RCT comparing vaccine types (29)	Pulmonary function status and clinical status
17	MRC advisory group (31)	1977	US	3 trials (111) RCT comparing vaccine and placebo	Antibody titres, seroconversion rates and seroprotection
18	Bartsch et al. (32)	1977	US	Live influenza vaccines RIT 4025 and RIT 4050, containing the recombinants of A/Scotland/840/74 and A/Victoria/3/75 with A/PR/8/34 virus	Pulmonary function status and clinical status
19	Prevost et al. (33)	1975	US	2 trials (44) Of different virus strains administered intranasally (LAIV)	Antibody titres, seroconversion rates and seroprotection
20	Fell et al. (34)	1977	US	Double blind RCT	Self-assessments of cough, breathlessness and wheeze
21	Howells and Tyler (35)	1961	US	RCT	Pneumonia and acute exacerbations of CLD and Pulmonary function status and clinical status

CLD- Chronic lung disease, ARI- Acute respiratory illness, RIT4025, 4050- vaccine strains.

Table 2. Outcomes and findings from randomized trials

Sample no	Study	n	Comparison	Outcome	Findings	Conclusion
Serological Outcome Measures and Pulmonary Function Tests (PFT)
1	Chuayachoo et al. (2010) (11)	160	Intradermal and Intramuscular vaccines	Geometric mean titres (H1N1)	Prevaccination (ID, IM) 23.5,199.1 Post vaccination (ID, IM) 22.1, 223.2	≥4-fold increase at 4 weeks Both routes effective
2	MRC advisory group (1977)	111	Live Vaccine and saline placebo	Actual serial titres reported	50% showed 4-fold increase in titres in vaccinated and none in unvaccinated	Effective increase in titres
3	Bartsch et al. (1977) (11)	-	2 live attenuated vaccines of different strains	Pulmonary function tests (PFT) 4 weeks	No change in PFT	Both vaccines were ineffective in improving PFT
4	Prevost et al. (1975) (33)	40	2 different strains of Intranasal vaccines	Seroconversion rates	86 and 73% for each vaccine in patients with low titres pre vaccination	Both had satisfactory antibody response
5	Gorse et al. (1997) (30)	29	Bivalent live attenuated influenza A virus vaccine (CAIIV) or saline solution placebo along with i.m. injection of IIV in both	Pulmonary function tests and antibody titres	No change in PFT Mean levels of anti-HA immunoglobulin A (IgA) antibodies in nasal washings increased significantly after vaccination with CAIIV and IIV compared to placebo	Increase in antibody titres but no change in PFT and clinical status
Clinical Outcome Measures
1	Kositanont et al. (2004) (13)	123	Live attenuated Vaccine and placebo	Lab diagnosed influenza	8.2% in vaccine group 27.4% in placebo	Significantly lower influenza in vaccinated
2	Wongsurakiat et al. (2004) (12)	125	Split virus vaccine and placebo	Influenza related ARI	6.8 and 28.1 per 100 persons years in vaccine and placebo groups	Significantly lower ARI in vaccinated
3	Gorse et al. (2003) (29)	2215	CAIVV- vaccine co administered with IIV3 and with placebo	Laboratory diagnosed Influenza Efficacy as1 minus hazard ratio	4.5% and 5.3% in vaccine and placebo groups No difference in Kaplan Meir curves, similar efficacy of 0.16 (95% CI: 0.22, 0.43)	Vaccine not compared to placebo but both vaccines effective
4	Furumoto et al. (2009)	167	23-valent PV + IIV and only IIV	Pneumonia and acute exacerbation of Chronic Lung Diseases (CLD)	0.53 episodes per patient year of infectious exacerbations 10.3% in PV+IIV and 26% in IV	Significantly lower exacerbations in the PV+IIV group compared with the IIV group but no difference for pneumonia

ARI-Acute Respiratory Infections, CAIVV-Cold-Adapted Influenza Virus Vaccine, IIV3- Trivalent Inactivated Influenza Virus Vaccine, PV- Pneumococcal Vaccine, IIV – Inactivated Influenza Vaccine.

Table 3. Outcomes and findings from observational studies

		Study		Design			N	Outcome measure	Finding	Conclusion
Hospitalizations and Acute Exacerbations Aas Outcome Measures
1		Seo et al. (2014) (21)	Case control, hospital controls matched 1:1 for age, gender, and date of hospital visit.			828		Hospitalization	Lower hospitalization among vaccinated: 33.7% (95% [CI] 14.0–49.0%; P = 0.002)	Significant reduction in hospitalizations
2		Montserrat-Capdevila et al. (2014) (22)	Retrospective cohort			1323		Hospitalization	Lower hospitalization among vaccinated: 68.4% (95%CI: 47.5–81.0)	Significant reduction in hospitalizations
3		Anar et al. (2010) (15)	Cross-sectional			82		Acute exacerbations requiring hospitalizations Antibody response	38.6% in vaccinated and 76.3% in unvaccinated, 50% of vaccinated had Increase IgG and IgA	Significantly fewer hospitalizations in vaccinated
4		Ayabe et al. (2009) (25)	Cohort			289		Acute exacerbation wheezing, pneumonia	11 of 189 (5.8%) in the vaccinated group and 23 of 100 (23%) in the unvaccinated group (RRR: relative risk reduction 74.7%, 95% CI: 0.5–0.87).	Significant reduction in acute exacerbations
5		Sumitani et al. (2009) (26)	Retrospective cohort additive inoculation of influenza vaccine (IIV) and 23-valent pneumococcal vaccine (PV)			-		Bacterial respiratory infections, number of hospitalizations, and length of hospital stay in the 2 years prior to and after PV inoculation.	3.16 vs. 1.95 infections; (p=0.0004) and 0.79 vs. 0.43 hospitalizations; (p=0.001) favour of vaccine	Significant reductions in acute infections
6		Menon et al. (2008) (14)	Cohort			87		Episodes and severity of ARI	The incidence of ARI 28.6 per 100 person-years prior to vaccination and 9.7 per 100 person-years post vaccination [relative risk (RR) 0.33; p = 0.005	Significant reductions in ARI
7		Karwat et al. (2007) (28) Karwat et al. is 2007 in Table 2 but 2006 in reference. Please correct year.</AQ>	Cohort			178		Acute exacerbations	The number of exacerbations decreased more than twice comparing the time before and after immunization: 1.7 ± 1.5 and 3.9 ± 2.4 per year, respectively	Reduction in acute exacerbations
Mortality as Outcome Measure
1	Kiyohara et al. (2013) (23)		Cohort – secondary data before and after law for vaccination		202 338 COPD deaths			Mortality from COPD	in January (RR 0.84; 95% CI 0.81-0.88), February (RR 0.85; 95% CI 0.81-0.89) and March (RR 0.92; 95% CI 0.88-0.96) among the population aged ≥ 65 years.	Reductions in mortality in elderly attributed to vaccination. However, in the population aged <65 years, statistically no significant changes in the COPD mortality rate were found in any month after the amendments were made
2	Schembri et al. (2009) (24)		Secondary data from The Health Improvement Network (THIN) database		177,120 patients with COPD			All-cause Mortality relative risks	Vaccinated – 0.30 (95% CI 0.28 to 0.32) and 0.98 (95% CI 0.96 to 1.11) and Unvaccinated - 0.59 (95% CI 0.57 to 0.61) during the influenza season and 0.97 (95% CI 0.94 to 1.00) outside the season	Significant reduction in all-cause mortality among vaccinated compared to not vaccinated
3	Wang et al. (2007) (16)		Retrospective cohort		35,637 patients with COPD			Mortality due to COPD in vaccinated	HR = 0.55	45% reduction in mortality in those vaccinated

Table 4. Vaccination coverage and its determinants

Study no	Authors	Year	Country	Study design	Sample	Findings
1	Vandenbos et al.	2013	France	Cross-sectional	476 patients, 246 with COPD	53% coverage
Refusal and intolerance reasons for no vaccination
2	Mowls et al.	2013	Australia	Cross- sectional	3108	31% (confidence interval 1.1, 1.6) more likely to have received an influenza vaccination in the past 12 months compared to those without a breathing test.
3	Ciblak et al.	2013	Turkey	Cross- sectional literature review	27 million at risk groups	14.9% coverage
Disbelief in effectiveness of vaccine
4	Santos-Sancho et al.	2013	Spain	Cross-sectional	European Health Survey (Spain) in 2009/10, data on 15,355 and 1,309 had COPD	49.4% coverage (95% CI: 46.3–52.5%) and 21.3% (95% CI: 20.7–21.9) among people without (p < 0.001).
Factors associated with an increase in vaccination coverage were: being male, perceiving one's health as fair or poor, not smoking, and having seen a doctor during the previous month.
5	Chiatti et al.	2013	Italy	Cross-sectional	5,935	30.5% coverage of adults (N = 670) and 74.8% (N = 2,796) of older people
Age increases the odds of vaccine uptake. Single marital status, Higher-education among the older people, smoking and not having contact with GPs in both age groups, are factors associated with non-vaccination.
6	Vozoris et al.	2009	Canada	Cross-sectional	134,072	47.9% coverage
Men, non-Ontarians, younger age groups, current smokers, and those without a family doctor were less likely to be vaccinated. Vaccine not necessary as reason
7	Schoefer et al.	2007	Germany	Cross-sectional	2131	46.5% coverage
Lack of information, patients' age and education level determinants
8	Jiménez-García et al.	2006	Catalonia, Spain	Cross-sectional	1783	62.5% coverage
Higher age, more frequent contact with the general practitioner and greater length of disease progression considerably increased
9	Jiménez-García et al.	2005	Spain	Cross-sectional	10711	Coverage 87.2%
More frequent contact with the general practitioner and a history of pneumococcal vaccination increase the likelihood of being vaccinated

Seo YB, Choi WS, Baek JH, et al.Effectiveness of the influenza vaccine at preventing hospitalization due to acute exacerbation of cardiopulmonary disease in Korea from 2011 to 2012. Hum Vaccin Immunother 2014; 10:423–427.

 PubMed Web of Science ®Google Scholar

Montserrat-Capdevila J, Godoy P, Marsal JR, Cruz I, Solanes M. [Effectiveness of influenza vaccination in preventing hospital admission due to exacerbations of chronic obstructive pulmonary disease]. Enferm Infecc Microbiol Clin 2014; 32:70–5.

 PubMed Web of Science ®Google Scholar

Kiyohara K, Kojimahara N, Sato Y, Yamaguchi N. Changes in COPD mortality rate after amendments to the Preventive Vaccination Law in Japan. Eur J Public Health 2013; 23:133–139.

 PubMed Web of Science ®Google Scholar

Anar C, Bicmen C, Yapicioglu S, Unsal I, Halilcolar H, Yilmaz U. Evaluation of clinical data and antibody response following influenza vaccination in patients with chronic obstructive pulmonary disease. New Microbiol 2010; 33:117–127.

 PubMed Web of Science ®Google Scholar

Chuaychoo B, Wongsurakiat P, Nana A, Kositanont U, Maranetra KN. The immunogenicity of intradermal influenza vaccination in COPD patients. Vaccine 2010; 28:4045–4051.

 PubMed Web of Science ®Google Scholar

Schembri S, Morant S, Winter JH, MacDonald TM. Influenza but not pneumococcal vaccination protects against all-cause mortality in patients with COPD. Thorax 2009; 64:567–572.

 PubMed Web of Science ®Google Scholar

Ayabe E, Kaneko N, Ohkuni Y, et al.[The efficacy of influenza vaccine for acute exacerbation of chronic obstructive lung disease in elderly patients]. Nihon Kokyuki Gakkai Zasshi 2008; 46:511–515.

 PubMedGoogle Scholar

Sumitani M, Tochino Y, Kamimori T, Fujiwara H, Fujikawa T. Additive inoculation of influenza vaccine and 23-valent pneumococcal polysaccharide vaccine to prevent lower respiratory tract infections in chronic respiratory disease patients. Intern Med 2008; 47:1189–1197.

 PubMed Web of Science ®Google Scholar

Furumoto A, Ohkusa Y, Chen M, et al.Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease. Vaccine 2008; 26:4284–4289.

 PubMed Web of Science ®Google Scholar

Menon B, Gurnani M, Aggarwal B. Comparison of outpatient visits and hospitalisations, in patients with chronic obstructive pulmonary disease, before and after influenza vaccination. Int J Clin Pract 2008; 62:593–598.

 PubMed Web of Science ®Google Scholar

Wang CS, Wang ST, Lai CT, Lin LJ, Chou P. Impact of influenza vaccination on major cause-specific mortality. Vaccine 2007; 25:1196–1203.

 PubMed Web of Science ®Google Scholar

Howells CH, Tyler LE. Prophylactic use of influenza vaccine in patients with chronic bronchitis. A pilot trial. Lancet 1961; 2:1428–1432.

 PubMed Web of Science ®Google Scholar

Karwat KJ, Szpotanska M, Szulc Z, Chazan R. [The influence of influenza vaccination on asthma and chronic obstructive pulmonary disease]. Pneumonol Alergol Pol 2006; 74:80–83.

 PubMedGoogle Scholar

Kositanont U, Kanyok R, Wasi C, Wongsurakiat P, Suthamsmai T, Maranetra N. Occurrence and protective level of influenza infections using serology in patients with COPD in vaccination study. J Med Assoc Thai 2004; 87:964–969.

 PubMedGoogle Scholar

Wongsurakiat P, Maranetra KN, Wasi C, Kositanont U, Dejsomritrutai W, Charoenratanakul S. Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study. Chest 2004; 125:2011–2020.

 PubMed Web of Science ®Google Scholar

Gorse GJ, O'Connor TZ, Young SL, et al.Efficacy trial of live, cold-adapted and inactivated influenza virus vaccines in older adults with chronic obstructive pulmonary disease: a VA cooperative study. Vaccine 2003; 21:2133–2144.

 PubMed Web of Science ®Google Scholar

Gorse GJ, Otto EE, Daughaday CC, et al.Influenza virus vaccination of patients with chronic lung disease. Chest 1997; 112:1221–1233.

 PubMed Web of Science ®Google Scholar

MRC Advisory Group on Pulmonary Function Tests. Trials of live attenuated influenza virus vaccine in patients with chronic obstructive airways disease. (MRC Advisory Group on Pulmonary Function Tests in relation to live influenza vaccines). Br J Dis Chest 1984; 78:236–247.

 PubMedGoogle Scholar

Bartsch P, Dierckx JP, Frans A, Gillard C, Jovanovic D, Stanescu D. Live influenza vaccine in patients with chronic bronchopulmonary diseases. A multicenter study with two consecutive vaccinal strains. Dev Biol Stand 1977; 39:113–121.

 PubMedGoogle Scholar

Prevost JM, Vereerstraeten-Schmerber J, Lamy F, De Koster JP. Live attenuated influenza virus vaccines in patients with chronic broncho-pulmonary diseases. Clinical and immunological evaluation. Scand J Respir Dis 1975; 56:58–69.

 PubMedGoogle Scholar

Fell PJ, Watson NP, O'Donnell HF, Simmons RL, Hasell SK. Longer term effects of live influenza vaccine in patients with chronic pulmonary disease. Lancet 1977; 1:1282–1284.

 PubMed Web of Science ®Google Scholar