Parental depression and their children's marriage timing: The long-term consequences of parental mental disorders.

Although decades of research documents powerful associations between parents' characteristics and their children's marital behaviors, the role of parental mental health has largely been ignored, despite the high prevalence of mental disorders and their strong potential to shape multiple dimensions of family life. Many studies examine other consequences of mothers' mental disorders, particularly for young children, but rarely do studies investigate the consequences of fathers' mental disorders, especially the potential for long-term consequences. We construct a theoretical framework for the study of intergenerational influences on family formation behaviors, integrating parental mental health, and emphasizing the potential for father's disorders to shape their children's lives. To investigate these associations, we use new intergenerational panel data featuring clinically validated diagnostic measures of parental mental health for both mothers and fathers, assessed independently. Results demonstrate that fathers' major depressive disorder is associated with significantly earlier marriage timing among sons. These important new findings provide insights into key priorities for social research on family formation processes and intergenerational influences across many domains.

The transition to parenthood, opportunity to drink, drinking, and alcohol use disorder.

BACKGROUND: This study used life histories from a setting of near universal marriage and childbearing (Nepal) to identify associations between both marital transitions and the transition into parenthood and alcohol use and disorder (AUD). METHODS: A retrospective, cross-sectional survey using life history calendars documented lifetime marital and childbearing histories of 4876 men and 5742 women aged 15-59 in 2016-18. The clinically validated, Nepal-specific Composite International Diagnostic Interview assessed first alcohol use opportunity, use, and disorder. RESULTS: Being never married increased the odds of having the opportunity to drink for men (OR=1.30, 95% CI=1.14 - 1.48, p < 0.001) and women (OR=1.24, 95% CI=1.08 - 1.43, p = 0.003) compared to being married. While men were never married, widowed, or divorced they were at a greater risk of developing AUD. The transition to parenthood significantly increased the odds of AUD onset for men (OR=1.71, 95% CI=1.12 - 2.61, p = 0.013), independent of marital transitions. For women in this setting, becoming divorced increased the odds of having their first drink (OR=1.77, 95% CI=1.14 - 2.75, p = 0.011). Giving birth to a first child also increased the odds of first opportunity to drink for women (OR=1.30, 95% CI=1.07 - 1.57, p = 0.008). CONCLUSIONS: We found associations between marital transitions and AUD that are consistent with findings worldwide. In this setting of near universal childbearing, the transition into fatherhood increased the odds of postpartum AUD among men.

Anti-IL-5 therapies for asthma.

BACKGROUND: This is the second update of previously published reviews in the Cochrane Library (2015, first update 2017). Interleukin-5 (IL-5) is the main cytokine involved in the proliferation, maturation, activation and survival of eosinophils, which cause airway inflammation and are a classic feature of asthma. Studies of monoclonal antibodies targeting IL-5 or its receptor (IL-5R) suggest they reduce asthma exacerbations, improve health-related quality of life (HRQoL) and lung function in appropriately selected patients, justifying their inclusion in the latest guidelines. OBJECTIVES: To compare the effects of therapies targeting IL-5 signalling (anti-IL-5 or anti-IL-5Rα) with placebo on exacerbations, health-related quality-of-life (HRQoL) measures and lung function in adults and children with chronic asthma, and specifically in those with eosinophilic asthma refractory to existing treatments. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers, manufacturers' websites, and reference lists of included studies. The most recent search was 7 February 2022. SELECTION CRITERIA: We included randomised controlled trials comparing mepolizumab, reslizumab and benralizumab versus placebo in adults and children with asthma. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and analysed outcomes using a random-effects model. We used standard methods expected by Cochrane. MAIN RESULTS: Seventeen studies on about 7600 participants met the inclusion criteria. Six used mepolizumab, five used reslizumab, and six used benralizumab. One study using benralizumab was terminated early due to sponsor decision and contributed no data. The studies were predominantly on people with severe eosinophilic asthma, which was similarly but variably defined. One was in children aged 6 to 17 years; nine others included children over 12 years but did not report results by age group separately. We deemed the overall risk of bias to be low, with all studies contributing data of robust methodology. We considered the certainty of the evidence for all comparisons to be high overall using the GRADE scheme, except for intravenous (IV) mepolizumab and subcutaneous (SC) reslizumab because these are not currently licensed delivery routes. The anti-IL-5 treatments assessed reduced rates of 'clinically significant' asthma exacerbation (defined by treatment with systemic corticosteroids for three days or more) by approximately half in participants with severe eosinophilic asthma on standard care (at least medium-dose inhaled corticosteroids (ICS)) with poorly controlled disease (either two or more exacerbations in the preceding year or Asthma Control Questionnaire (ACQ) score of 1.5 or more), except for reslizumab SC. The rate ratios for these effects were 0.45 (95% confidence interval (CI) 0.36 to 0.55; high-certainty evidence) for mepolizumab SC, 0.53 (95% CI 0.44 to 0.64; moderate-certainty evidence) for mepolizumab IV, 0.43 (95% CI 0.33 to 0.55; high-certainty evidence) for reslizumab IV, and 0.59 (95% CI 0.52 to 0.66; high-certainty evidence) for benralizumab SC. Non-eosinophilic participants treated with benralizumab also showed a significant reduction in exacerbation rates, an effect not seen with reslizumab IV, albeit in only one study. No data were available for non-eosinophilic participants treated with mepolizumab. There were improvements in validated HRQoL scores with all anti-IL-5 agents in severe eosinophilic asthma. This met the minimum clinically important difference (MCID) for the broader St. George's Respiratory Questionnaire (SGRQ; 4-point change) for benralizumab only, but the improvement in the ACQ and Asthma Quality of Life Questionnaire (AQLQ), which focus on asthma symptoms, fell short of the MCID (0.5 point change for both ACQ and AQLQ) for all of the interventions. The evidence for an improvement in HRQoL scores in non-eosinophilic participants treated with benralizumab and reslizumab was weak, but the tests for subgroup difference were negative. All anti-IL-5 treatments produced small improvements in mean pre-bronchodilator forced expiratory flow in one second (FEV1) of between 0.08 L and 0.15 L in eosinophilic participants, which may not be sufficient to be detected by patients. There were no excess serious adverse events with any anti-IL-5 treatment; in fact, there was a reduction in such events with benralizumab, likely arising from fewer asthma-related hospital admissions. There was no difference compared to placebo in adverse events leading to discontinuation with mepolizumab or reslizumab, but significantly more discontinued benralizumab than placebo, although the absolute numbers were small (42/2026 (2.1%) benralizumab versus 11/1227 (0.9%) placebo). The implications for efficacy or adverse events are unclear. AUTHORS' CONCLUSIONS: Overall this analysis supports the use of anti-IL-5 treatments as an adjunct to standard care in people with severe eosinophilic asthma and poor symptom control. These treatments roughly halve the rate of asthma exacerbations in this population. There is limited evidence for improved HRQoL scores and lung function, which may not meet clinically detectable levels. The studies did not report safety concerns for mepolizumab or reslizumab, or any excess serious adverse events with benralizumab, although there remains a question over adverse events significant enough to prompt discontinuation. Further research is needed on biomarkers for assessing treatment response, optimal duration and long-term effects of treatment, risk of relapse on withdrawal, non-eosinophilic patients, children (particularly under 12 years), comparing anti-IL-5 treatments to each other and, in patients meeting relevant eligibility criteria, to other biological (monoclonal antibody) therapies. For benralizumab, future studies should closely monitor rates of adverse events prompting discontinuation.

ANTECEDENTES: Esta la segunda actualización de una revisión publicada anteriormente en la Biblioteca Cochrane (2015, primera actualización en 2017). La interleucina 5 (IL­5) es la principal citoquina implicada en la proliferación, maduración, activación y supervivencia de los eosinófilos, que provocan la inflamación de las vías respiratorias y son una característica típica del asma. Los estudios sobre los anticuerpos monoclonales dirigidos a la IL­5 o a su receptor (IL­5R) indican que estos reducen las exacerbaciones del asma, mejoran la calidad de vida relacionada con la salud (CdVRS) y la función pulmonar en pacientes adecuadamente seleccionados, lo cual justifica su inclusión en las últimas guías. OBJETIVOS: Comparar los efectos de los tratamientos dirigidos a la señalización de la IL­5 (anti­IL­5 o anti­IL­5Rα) con placebo, con respecto a las exacerbaciones, las medidas de calidad de vida relacionada con la salud (CdVRS) y la función pulmonar en adultos y niños con asma crónica, y específicamente en los que presentan asma eosinofílica resistente a los tratamientos existentes. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en CENTRAL, MEDLINE, Embase, y en dos registros de ensayos clínicos, sitios web de fabricantes y listas de referencias de los estudios incluidos. La búsqueda más reciente se realizó el 7 de febrero de 2022. CRITERIOS DE SELECCIÓN: Se incluyeron ensayos controlados aleatorizados que compararon mepolizumab, reslizumab y benralizumab versus placebo en adultos y niños con asma. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión de forma independiente extrajeron los datos y analizaron los desenlaces mediante un modelo de efectos aleatorios. Se utilizaron los métodos estándar previstos por Cochrane. RESULTADOS PRINCIPALES: Diecisiete estudios con unos 7600 participantes cumplieron los criterios de inclusión. Seis administraron mepolizumab, cinco proporcionaron reslizumab y seis benralizumab. Un estudio que utilizó benralizumab finalizó antes de tiempo por decisión de los patrocinadores y no proporcionó datos. Los estudios se realizaron principalmente en personas con asma eosinofílica grave, que se definió de forma parecida aunque variable. Uno de ellos se realizó en niños de seis a 17 años; otros nueve incluyeron a niños mayores de 12 años, pero no informaron de los resultados por grupos de edad por separado. Se consideró que el riesgo general de sesgo fue bajo, ya que todos los estudios que aportaron datos tuvieron una metodología sólida. La certeza de la evidencia para todas las comparaciones fue en general alta al utilizar el método GRADE, con la excepción del mepolizumab intravenoso (IV) y subcutáneo (SC) porque se trata de vías de administración no autorizadas en la actualidad. Los tratamientos con inhibidores de la IL­5 evaluados redujeron las tasas de exacerbación del asma "clínicamente significativa" (definida por el tratamiento con corticosteroides sistémicos durante tres días o más) en aproximadamente la mitad de los participantes con asma eosinofílica grave que recibían atención estándar (al menos una dosis media de corticosteroides inhalados [CSI]) con un control deficiente de la enfermedad (dos o más exacerbaciones en el año anterior o una puntuación de 1,5 o más según el Asthma Control Questionnaire [ACQ]). Los cocientes de tasas para estos efectos fueron de 0,45 (intervalo de confianza [IC] del 95%: 0,36 a 0,55; evidencia de certeza alta) para mepolizumab SC, 0,53 (IC del 95%: 0,44 a 0,64; evidencia de certeza moderada) para mepolizumab IV, 0,43 (IC del 95%: 0,33 a 0,55; evidencia de certeza alta) para reslizumab IV y 0,59 (IC del 95%: 0,52 a 0,66; evidencia de certeza alta) para benralizumab SC. Los participantes que no presentaban asma eosinofílica tratados con benralizumab también mostraron una reducción significativa de las tasas de exacerbaciones, un efecto que no se observó con reslizumab IV, aunque solo en un estudio. No hubo datos sobre los participantes que no presentaban asma eosinofílica tratados con mepolizumab. Hubo mejorías moderadas en las puntuaciones validadas de la CdVRS con todos los inhibidores de la IL­5 en el asma eosinofílica grave. Se alcanzó la diferencia mínima clínicamente importante (DMCI) del George's Respiratory Questionnaire (SGRQ; cambio de 4 puntos) para benralizumab, pero la mejoría en el ACQ y el Asthma Quality of Life Questionnaire (AQLQ), que se centran en los síntomas del asma, no alcanzó la DMCI (cambio de 0,5 puntos tanto en el ACQ como en el AQLQ) para todas las intervenciones. La evidencia fue débil en cuanto a la mejoría en las puntuaciones de la CdVRS en los participantes que no presentaban asma eosinofílica tratados con benralizumab y reslizumab, pero los análisis de las diferencias de subgrupos obtuvieron resultados negativos. Todos los tratamientos con inhibidores de la IL­5 produjeron pequeñas mejorías en el flujo espiratorio forzado prebroncodilatador en un segundo (VEF1) de entre 0,08 y 0,15 l en los participantes con asma eosinofílica, las cuales podrían no ser suficientes para que los pacientes las detecten. No hubo un exceso de eventos adversos graves con ningún tratamiento inhibidor de la IL­5; de hecho, hubo una reducción de tales eventos con benralizumab, probablemente derivada de un menor número de ingresos hospitalarios relacionados con el asma. No hubo diferencias en comparación con placebo en los eventos adversos que provocaran la suspensión del tratamiento con mepolizumab o reslizumab, pero hubo significativamente más interrupciones con el benralizumab que con placebo, aunque los números absolutos fueron pequeños (42/2026 [2,1%] benralizumab versus 11/1227 [0,9%] placebo). No están claras las implicaciones con respecto a la eficacia o los eventos adversos. CONCLUSIONES DE LOS AUTORES: En general este análisis apoya la administración de los tratamientos inhibidores de la IL­5 como complemento a la atención estándar en las personas con asma eosinofílica grave y un control deficiente de los síntomas. Estos tratamientos reducen a cerca de la mitad la tasa de exacerbaciones del asma en esta población. Hay evidencia limitada de mejorías en las puntuaciones de la CdVRS y en la función pulmonar, aunque es posible que no alcancen niveles clínicamente detectables. Los estudios no informaron de problemas de seguridad con el mepolizumab ni el reslizumab, ni eventos adversos graves excesivos con benralizumab, aunque se mantiene la duda sobre qué eventos adversos son lo suficientemente significativos para la suspensión inmediata. Se necesitan estudios de investigación adicionales sobre los marcadores biológicos para evaluar la respuesta al tratamiento, la duración óptima y los efectos a largo plazo del tratamiento, el riesgo de recurrencia al retirarlo, los pacientes que no presentan asma eosinofílica, los niños (especialmente menores de 12 años), que comparen los tratamientos inhibidores de la IL­5 entre sí y, en pacientes que cumplan criterios de elegibilidad relevantes, con otros tratamientos biológicos (anticuerpos monoclonales). En el caso del benralizumab, los estudios futuros deben vigilar atentamente las tasas de eventos adversos que provocan la interrupción inmediata.

Prevalence and incidence of neuromuscular conditions in the UK between 2000 and 2019: A retrospective study using primary care data.

BACKGROUND: In the UK, large-scale electronic primary care datasets can provide up-to-date, accurate epidemiological information on rarer diseases, where specialist diagnoses from hospital discharges and clinic letters are generally well recorded and electronically searchable. Current estimates of the number of people living with neuromuscular disease (NMD) have largely been based on secondary care data sources and lacked direct denominators. OBJECTIVE: To estimate trends in the recording of neuromuscular disease in UK primary care between 2000-2019. METHODS: The Clinical Practice Research Datalink (CPRD) database was searched electronically to estimate incidence and prevalence rates (per 100,000) for a range of NMDs in each year. To compare trends over time, rates were age standardised to the most recent CPRD population (2019). RESULTS: Approximately 13 million patients were actively registered in each year. By 2019, 28,230 active patients had ever received a NMD diagnosis (223.6), which was higher among males (239.0) than females (208.3). The most common classifications were Guillain-Barre syndrome (40.1), myasthenia gravis (33.7), muscular dystrophy (29.5), Charcot-Marie-Tooth (29.5) and inflammatory myopathies (25.0). Since 2000, overall prevalence grew by 63%, with the largest increases seen at older ages (≥65-years). However, overall incidence remained constant, though myasthenia gravis incidence has risen steadily since 2008, while new cases of muscular dystrophy fell over the same period. CONCLUSIONS: Lifetime recording of many NMDs on primary care records exceed current estimates of people living with these conditions; these are important data for health service and care planning. Temporal trends suggest this number is steadily increasing, and while this may partially be due to better recording, it cannot be simply explained by new cases, as incidence remained constant. The increase in prevalence among older ages suggests increases in life expectancy among those living with NMDs may have occurred.

Digital interventions for the management of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with dyspnoea, cough or sputum production (or both) and affects quality of life and functional status. More efficient approaches to alternative management that may include patients themselves managing their condition need further exploration in order to reduce the impact on both patients and healthcare services. Digital interventions may potentially impact on health behaviours and encourage patient engagement. OBJECTIVES: To assess benefits and harms of digital interventions for managing COPD and apply Behaviour Change Technique (BCT) taxonomy to describe and explore intervention content. SEARCH METHODS: We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search 28 April 2020). We found other trials at web-based clinical trials registers. SELECTION CRITERIA: We included RCTs comparing digital technology interventions with or without routine supported self-management to usual care, or control treatment for self-management. Multi-component interventions (of which one component was digital self-management) compared with usual care, standard care or control treatment were included. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Two review authors independently selected trials for inclusion, extracted data, and assessed risk of bias. Discrepancies were resolved with a third review author. We assessed certainty of the evidence using the GRADE approach. Primary outcomes were impact on health behaviours, self-efficacy, exacerbations and quality of life, including the St George's Respiratory Questionnaire (SGRQ). The minimally important difference (MID) for the SGRQ is 4 points. Two review authors independently applied BCT taxonomy to identify mechanisms in the digital interventions that influence behaviours. MAIN RESULTS: Fourteen studies were included in the meta-analyses (1518 participants) ranging from 13 to 52 weeks duration. Participants had mild to very severe COPD. Risk of bias was high due to lack of blinding. GRADE ratings were low to very low certainty due to lack of blinding and imprecision. Common BCT clusters identified as behaviour change mechanisms in interventions were goals and planning, feedback and monitoring, social support, shaping knowledge and antecedents. Digital technology intervention with or without routine supported self-management Interventions included mobile phone (three studies), smartphone applications (one study), and web or Internet-based (five studies). Evidence is very uncertain about effects on impact on health behaviours as measured by six-minute walk distance (6MWD) at 13 weeks (mean difference (MD) 26.20, 95% confidence interval (CI) -21.70 to 74.10; participants = 122; studies = 2) or 23 to 26 weeks (MD 14.31, 95% CI -19.41 to 48.03; participants = 164; studies = 3). There may be improvement in 6MWD at 52 weeks (MD 54.33 95% CI -35.47 to 144.12; participants = 204; studies = 2) but studies were varied (very low certainty). There may be no difference in self-efficacy on managing Chronic Disease Scale (SEMCD) or pulmonary rehabilitation adapted index of self-efficacy tool (PRAISE). Evidence is very uncertain. Quality of life may be slightly improved on the chronic respiratory disease questionnaire (CRQ) at 13 weeks (MD 0.45, 95% CI 0.01 to 0.90; participants = 123; studies = 2; low certainty), but is not clinically important (MID 0.5). There may be little or no difference at 23 or 52 weeks (low to very low certainty). There may be a clinical improvement on SGRQ total at 52 weeks (MD -26.57, 95% CI -34.09 to -19.05; participants = 120; studies = 1; low certainty). Evidence for COPD assessment test (CAT) and Clinical COPD Questionnaire (CCQ) is very uncertain. There may be little or no difference in dyspnoea symptoms (CRQ dyspnoea) at 13, 23 weeks or 52 weeks (low to very low certainty evidence) or mean number of exacerbations at 26 weeks (low-certainty evidence). There was no evidence for the number of people experiencing adverse events. Multi-component interventions Digital components included mobile phone (one study), and web or internet-based (four studies). Evidence is very uncertain about effects on impact on health behaviour (6MWD) at 13 weeks (MD 99.60, 95% CI -15.23 to 214.43; participants = 20; studies = 1). No evidence was found for self-efficacy. Four studies reported effects on quality of life (SGRQ and CCQ scales). The evidence is very uncertain. There may be no difference in the number of people experiencing exacerbations or mean days to first exacerbation at 52 weeks with a multi-component intervention compared to standard care. Evidence is very uncertain about effects on the number of people experiencing adverse events at 52 weeks. AUTHORS' CONCLUSIONS: There is insufficient evidence to demonstrate a clear benefit or harm of digital technology interventions with or without supported self-management, or multi-component interventions compared to usual care in improving the 6MWD or self-efficacy. We found there may be some short-term improvement in quality of life with digital interventions, but there is no evidence about whether the effect is sustained long term. Dyspnoea symptoms may improve over a longer duration of digital intervention use. The evidence for multi-component interventions is very uncertain and as there is little or no evidence for adverse events, we cannot determine the benefit or harm of these interventions. The evidence base is predominantly of very low certainty with concerns around high risk of bias due to lack of blinding. Given that variation of interventions and blinding is likely to be a concern, future, larger studies are needed taking these limitations in consideration. Future studies are needed to determine whether the small improvements observed in this review can be applied to the general COPD population. A clear understanding of behaviour change through the BCT classification is important to gauge uptake of digital interventions and health outcomes in people with varying severity of COPD. Currently there is no guidance for interpreting BCT components of a digital intervention for changes to health outcomes. We could not interpret the BCT findings to the health outcomes we were investigating due to limited evidence that was of very low certainty. In future research, standardised approaches need to be considered when designing protocols to investigate effectiveness of digital interventions by including a standardised approach to BCT classification in addition to validated behavioural outcome measures that may reflect changes in behaviour.

Anti-IL-5 therapies for chronic obstructive pulmonary disease.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of hospital admissions, disease-related morbidity and mortality. COPD is a heterogeneous disease with distinct inflammatory phenotypes, including eosinophilia, which may drive acute exacerbations in a subgroup of patients. Monoclonal antibodies targeting interleukin 5 (IL-5) or its receptor (IL-5R) have a role in the care of people with severe eosinophilic asthma, and may similarly provide therapeutic benefit for people with COPD of eosinophilic phenotype. OBJECTIVES: To assess the efficacy and safety of monoclonal antibody therapies targeting IL-5 signalling (anti-IL-5 or anti-IL-5Rα) compared with placebo in the treatment of adults with COPD. SEARCH METHODS: We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, clinical trials registries, manufacturers' websites, and reference lists of included studies. Our most recent search was 23 September 2020. SELECTION CRITERIA: We included randomised controlled trials comparing anti-IL-5 therapy with placebo in adults with COPD. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and analysed outcomes using a random-effects model.The primary outcomes were exacerbations requiring antibiotics or oral steroids, hospitalisations due to exacerbation of COPD, serious adverse events, and quality of life. We used standard methods expected by Cochrane. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: Six studies involving a total of 5542 participants met our inclusion criteria. Three studies used mepolizumab (1530 participants), and three used benralizumab (4012 participants). The studies were on people with COPD, which was similarly defined with a documented history of COPD for at least one year. We deemed the risk of bias to be generally low, with all studies contributing data of robust methodology. Mepolizumab 100 mg reduces the rate of moderate or severe exacerbations by 19% in those with an eosinophil count of at least 150/µL (rate ratio (RR) 0.81, 95% confidence interval (CI) 0.71 to 0.93; participants = 911; studies = 2, high-certainty evidence). When participants with lower eosinophils are included, mepolizumab 100 mg probably reduces the exacerbation rate by 8% (RR 0.92, 95% CI 0.82 to 1.03; participants = 1285; studies = 2, moderate-certainty evidence). Mepolizumab 300 mg probably reduces the rate of exacerbations by 14% in participants all of whom had raised eosinophils (RR 0.86, 95% CI 0.70 to 1.06; participants = 451; studies = 1, moderate-certainty evidence); the evidence was uncertain for a single small study of mepolizumab 750 mg. In participants with high eosinophils, mepolizumab probably reduces the rate of hospitalisation by 10% (100 mg, RR 0.90, 95% CI 0.65 to 1.24; participants = 911; studies = 2, moderate-certainty evidence) and 17% (300 mg, RR 0.83, 95% CI 0.51 to 1.35; participants = 451; studies = 1, moderate-certainty evidence). Mepolizumab 100 mg increases the time to first moderate or severe exacerbation compared to the placebo group, in people with the eosinophilic phenotype (hazard ratio (HR) 0.78, 95% CI 0.66 to 0.92; participants = 981; studies 2, high-certainty evidence). When participants with lower eosinophils were included this difference was smaller and less certain (HR 0.87, 95% CI 0.75 to 1.0; participants = 1285; studies 2, moderate-certainty evidence). Mepolizumab 300 mg probably increases the time to first moderate or severe exacerbation in participants who all had eosinophilic phenotype (HR 0.77, 95% CI 0.60 to 0.99; participants = 451; studies = 1, moderate-certainty evidence). Benralizumab 100 mg reduces the rate of severe exacerbations requiring hospitalisation in those with an eosinophil count of at least 220/µL (RR 0.63, 95% CI 0.49 to 0.81; participants = 1512; studies = 2, high-certainty evidence). Benralizumab 10 mg probably reduces the rate of severe exacerbations requiring hospitalisation in those with an eosinophil count of at least 220/µL (RR 0.68, 95% CI 0.49 to 0.94; participants = 765; studies = 1, moderate-certainty evidence). There was probably little or no difference between the intervention and placebo for quality of life measures. Where there were differences the mean difference fell below the pre-specified minimum clinically significant difference. Treatment with mepolizumab and benralizumab appeared to be safe. All pooled analyses showed that there was probably little or no difference in serious adverse events, adverse events, or side effects between the use of a monoclonal antibody therapy compared to placebo. AUTHORS' CONCLUSIONS: We found that mepolizumab and benralizumab probably reduce the rate of moderate and severe exacerbations in the highly selected group of people who have both COPD and higher levels of blood eosinophils. This highlights the importance of disease phenotyping in COPD, and may play a role in the personalised treatment strategy in disease management. Further research is needed to elucidate the role of monoclonal antibodies in the management of COPD in clinical practice. In particular, it is not clear whether there is a threshold blood eosinophil level above which these drugs may be effective. Studies including cost effectiveness analysis may be beneficial given the high cost of these therapies, to support use if appropriate.