Improving access to affordable quality-assured inhaled medicines in low- and middle-income countries.

BACKGROUND: Access to affordable inhaled medicines for chronic respiratory diseases (CRDs) is severely limited in low- and middle-income countries (LMICs), causing avoidable morbidity and mortality. The International Union Against Tuberculosis and Lung Disease convened a stakeholder meeting on this topic in February 2022.METHODS: Focused group discussions were informed by literature and presentations summarising experiences of obtaining inhaled medicines in LMICs. The virtual meeting was moderated using a topic guide around barriers and solutions to improve access. The thematic framework approach was used for analysis.RESULTS: A total of 58 key stakeholders, including patients, healthcare practitioners, members of national and international organisations, industry and WHO representatives attended the meeting. There were 20 pre-meeting material submissions. The main barriers identified were 1) low awareness of CRDs; 2) limited data on CRD burden and treatments in LMICs; 3) ineffective procurement and distribution networks; and 4) poor communication of the needs of people with CRDs. Solutions discussed were 1) generation of data to inform policy and practice; 2) capacity building; 3) improved procurement mechanisms; 4) strengthened advocacy practices; and 5) a World Health Assembly Resolution.CONCLUSION: There are opportunities to achieve improved access to affordable, quality-assured inhaled medicines in LMICs through coordinated, multi-stakeholder, collaborative efforts.

Household air pollution and COPD: cause and effect or confounding by other aspects of poverty?

SETTING: Household air pollution (HAP) and chronic obstructive pulmonary disease (COPD) are both major public health problems, reported to cause around 4 million and 3 million deaths every year, respectively. The great majority of these deaths, as well as the burden of disease during life is felt by people in low- and middle-income countries (LMICs).OBJECTIVE and DESIGN: The extent to which HAP causes COPD is controversial; we therefore undertook this review to offer a viewpoint on this from the Global Initiative for COPD (GOLD).RESULTS: We find that while COPD is well-defined in many studies on COPD and HAP, there are major limitations to the definition and measurement of HAP. It is thus difficult to disentangle HAP from other features of poverty that are themselves associated with COPD. We identify other limitations to primary research studies, including the use of cross-sectional designs that limit causal inference.CONCLUSION: There is substantial preventable morbidity and mortality associated with HAP, COPD and poverty, separately and together. Although it may not be possible to define clear causal links between HAP and COPD, there is a clear urgency to reduce the avoidable burden of disease these inflict on the world´s poor.

The GOLD Summit on chronic obstructive pulmonary disease in low- and middle-income countries.

Chronic obstructive pulmonary disease (COPD) is one of the top three causes of death worldwide, but governments and non-governmental organisations have not given its prevention and treatment the priority it requires. This is particularly true in low- and middle-income countries, where most of the people suffering from this disease live. The United Nations (UN) has targeted a reduction of premature deaths from non-communicable diseases (NCDs) by a third by 2030; however, a coordinated UN/World Health Organization (WHO) strategy to address the burden of COPD (one of the most important NCDs) is still lacking. To explore the extent of the problem and inform the development of policies to improve the situation, the Board of Directors of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) held a 1-day Summit. The key themes that emerged were the need to ensure accurate data on prevalence, raise awareness of the disease among the public, healthcare professionals and governments, including the fact that COPD aetiology goes beyond smoking (and other inhaled pollutants) and includes poor lung development in early life, and ensure that spirometry and both pharmacological and non-pharmacological therapies are available and affordable. Here, we present the actions that must be taken to address the impact of COPD. We believe that the WHO is particularly well-positioned to co-ordinate an attack on COPD, and GOLD will do all it can to help and rally support.

Budesonide/formoterol vs. salmeterol/fluticasone in COPD: a systematic review and adjusted indirect comparison of pneumonia in randomised controlled trials.

AIMS: This analysis was designed to provide a comparison between budesonide/formoterol and salmeterol/fluticasone for the relative incidence of pneumonia adverse events, pneumonia serious adverse events and pneumonia-related mortality in patients being treated for chronic obstructive pulmonary disease. METHODS: An initial literature search revealed no suitable head-to-head trials between budesonide/formoterol and salmeterol/fluticasone and therefore a systematic review was conducted to find randomised controlled trials providing data for input into an adjusted indirect comparison of the two combination treatments using placebo as a common comparator. The Bucher adjusted indirect comparison method was used to calculate odds ratios and 95% confidence intervals. RESULTS: Eight salmeterol/fluticasone trials and four budesonide/formoterol trials were identified as being relevant for the analyses. The proportion of patients experiencing a pneumonia adverse event was significantly lower with budesonide/formoterol than salmeterol/fluticasone (odds ratio, 0.47; 95% confidence interval, 0.28-0.80). The proportion of patients experiencing a pneumonia serious adverse event was also significantly lower with budesonide/formoterol than salmeterol/fluticasone (odds ratio, 0.41; 95% confidence interval, 0.19-0.86). However, there were too few events to draw any firm conclusions on pneumonia-related mortality. CONCLUSIONS: The results of the indirect comparison support the hypothesis that budesonide/formoterol is associated with fewer pneumonia events than salmeterol/fluticasone in chronic obstructive pulmonary disease. The limitations of the analysis are that the results from a single study, TORCH, have a large bearing on the overall findings of the analysis, and that there is heterogeneity in the length and the dosing of the included studies, although it does not appear that heterogeneity affected the reported results. Another important limitation is the lack of predefined diagnostic standards for pneumonia in these studies.

Stratification of COPD patients by previous admission for targeting of preventative care.

BACKGROUND: Hospital admissions for exacerbations of chronic obstructive pulmonary disease (COPD) impact considerably on disease evolution and healthcare provision. Building on previous studies, this study postulated that COPD patients could be stratified by risk of admission to determine which groups provide the greatest burden on resources, and how interventions should be targeted to prevent admissions. METHODS: COPD admissions during 1997-2003 in three Strategic Health Authorities in England were analysed (n=80,291). Patients admitted during winter (1 November-31 March) were stratified into three groups according to the number of admissions during the previous year: 0 (NIL), 1-2 (MOD) or >or=3 (FRQ). Winter weeks were classified as "average", "above average", "high", or "very high" risk, compared with the long-term mean. RESULTS: The risk of admission during winter for FRQ and MOD patients was 40% and 12% respectively. NIL patients contributed to 70% of winter admissions, and 90% of the variation between "average" and "very high" weeks, versus 9% and 1% for MOD and FRQ. CONCLUSIONS: Patients with no previous admissions have lower individual risk, but contribute to a high overall utilisation of health care resources and should be targeted to prevent admissions. Focusing upon high-risk patients (frequent attenders or more severe) may only reduce a small proportion of admissions, and therefore clinicians should ensure that all COPD patients receive appropriate therapy to reduce risk of exacerbations.

Confidence and understanding among general practitioners and practice nurses in the UK about diagnosis and management of COPD.

In order to assess the confidence of healthcare professionals in diagnosing and managing COPD telephone interviews were conducted with 60 practice nurses and 46 general practitioners (GPs) in 2001 and 61 nurses and 39 GPs in 2005. The nurses all ran respiratory clinics. 80% of GPs were confident about diagnosing COPD and this had increased from 52% in 2001. Fifty five percent of nurses were confident and there was no change from 2001. In 2005, 79% of GPs and 70% of nurses were confident about differentiating asthma and COPD. Smoking history, breathlessness, age of onset, lack of response to asthma therapy and cough were reported as features differentiating COPD from asthma. Most respondents stated that spirometry is essential to diagnose COPD and in 2005 nearly all practices had access to a spirometry service. GPs were more confident about interpreting spirometry results in 2005 than nurses and their confidence had increased significantly from 2001. In 2005, nearly all respondents had heard of pulmonary rehabilitation, and significantly more had a programme in their area in 2005 than 2001 (69% vs. 49% p=0.05). Fifty four percent of GPs were confident about which patients to refer for long term oxygen therapy in 2005 but nurses were less confident. There had not been any significant change between 2001 and 2005. In 2005 only 35% of respondents had access to a pulse oximeter. When presented with case scenarios, GPs self-reported confidence was not reflected in their diagnoses or investigation and management strategies and they seem to favour cardiac over respiratory diagnoses.

Evaluating the effectiveness of combination therapy to prevent COPD exacerbations: the value of NNT analysis.

The effective prevention of exacerbations in patients with chronic obstructive pulmonary disease (COPD) has the potential to improve patients' health-related quality of life, reduce rates of hospitalisation and mortality and lower healthcare costs. Several pharmacological agents, including inhaled corticosteroid/long-acting beta2-agonist combination therapies, have demonstrated beneficial effects on COPD exacerbations. The number needed to treat (NNT) analysis is a simple, concise method that allows physicians to quantify directly the benefits that alternative treatment options have on disease outcomes in terms of the number of patients who need to be treated before a benefit is observed. This review evaluates the applicability and clinical relevance of NNT analysis for determining the effectiveness of combination therapies against COPD exacerbations, focusing on budesonide/ formoterol in the same inhaler. Physicians are encouraged to consider NNT data within the context of their limitations and in conjunction with other analytical methods when selecting treatments for patients with COPD.

Living with severe chronic obstructive pulmonary disease (COPD): perceptions of patients and their carers. An interpretative phenomenological analysis.

BACKGROUND: A study designed to explore the experiences of patients with severe chronic obstructive pulmonary disease (COPD) and their carers, particularly with regard to ongoing and palliative care needs. METHODS: The participants were nine men and one woman with severe COPD and the carers of eight of the men, in East Devon, UK. Semi-structured interviews were undertaken, transcribed and analysed using interpretative phenomenological analysis (IPA). RESULTS: The emergent themes were of losses, adaptation, relationships with health professionals and effect on carer. Losses reflected the loss of personal liberty and dignity and of previous expectations of the future. Adaptation included strategies to cope with the effects of the disease. Relationships related to both positive and negative aspects of contact with health professionals. There was appreciation for continuity of care and reassurance. The effect on the carer was evident particularly as they had to take on multiple roles. They also experienced some of the same losses as the patient and appeared enmeshed with the illness. CONCLUSIONS: This study confirmed the inexorable decline in activities of daily life and social isolation for patients with severe COPD. Adaptive strategies were common and some positive aspects were identified. Support from the primary health care team was appreciated. The strain on carers was very apparent. The concept of a more structured sharing of information and a surveillance role mediated by health care professionals known to the patient and carer would be a pragmatic approach to improving care.

Attack context: an important mediator of the relationship between psychological status and asthma outcomes.

BACKGROUND: The importance of psychosocial variables in asthma is increasingly recognised, although attempts to relate these to asthma outcomes often produce only weak relationships. This study aimed to identify whether such relationships might be obscured by the effects of recent asthma experience on psychological status. METHODS: An adult community sample of 37 patients who had suffered a recent attack of asthma and 37 with stable asthma were given measures of panic fear and control confidence. The relationship with subsequent emergency service use was examined using two way ANOVA and correlational analyses. Covariate influences (psychiatric morbidity, age, sex, treatment level, asthma duration, social status) were considered. RESULTS: Control confidence predicted emergency service use in different ways for recent attack and stable asthma patients. This interaction was highly significant (F(1,69) = 10.32, p<0.005) with high confidence relating to an increased risk of an attack in the recent attack group and low confidence relating to increased risk for the stable asthma group. There was also an interaction between panic fear and attack context (F(1,69) = 11.05, p<0.005) with low panic fear resulting in more attacks for recent attack cases. CONCLUSIONS: Attack context (having a recent attack) is an important mediator of psychological status. Strong cognitive/affective responses to attacks may motivate improved self-care and this represents a window of opportunity for self-care interventions. Weak cognitive/affective responses to attacks may reflect denial and require different intervention approaches. For those with recently stable asthma the relationships are qualitatively and quantitatively different, and the implications for intervention are also discussed.

Asthma after childhood pneumonia: six year follow up study.

OBJECTIVE: To establish the long term cumulative prevalence of asthma in children admitted to hospital with pneumonia and to examine the hypothesis that some children admitted to hospital with pneumonia may be presenting with undiagnosed asthma. DESIGN: Prospective study of a cohort of children previously admitted to hospital with pneumonia, followed up by postal questionnaires to their general practitioners and the children or their parents. SETTING: General practices in southwest England. PARTICIPANTS: 78 children admitted to the Royal Devon and Exeter Hospital between 1989 and 1991 with a diagnosis of pneumonia confirmed on independent review of x ray films. MAIN OUTCOME MEASURES: Any diagnosis of asthma, use of any treatment for asthma, and asthma symptom scores. RESULTS: On the basis of a 100% response rate from general practitioners and 86% from patients or parents, the cumulative prevalence of asthma was 45%. A diagnosis of asthma was associated with a family history of asthma (odds ratio 11.23; 95% confidence interval 2.57 to 56.36; P=0.0002). Mean symptom scores were higher for all children with asthma (mean score 2.4; chi(2)=14.88; P=0. 0001) and for children with asthma not being treated (mean 1.4; chi(2)=6.2; P=0.01) than for those without asthma (mean 0.2). CONCLUSIONS: A considerable proportion of children presenting to a district general hospital with pneumonia either already have unrecognised asthma or subsequently develop asthma. The high cumulative prevalence of asthma suggests that careful follow up of such children is worth while. Asthma is undertreated in these children; a structured symptom questionnaire may help to identify and reduce morbidity due to undertreatment.

Home treatment of patients with cystic fibrosis using the 'Intermate': the first year's experience.

Home treatment of patients with cystic fibrosis has many attractions and is becoming increasingly popular. The investigators have studied the use, results and costs of the first year of operation of a home-care intravenous antibiotic service using the 'Intermate' infusion device in a prospective study using questionnaires, spirometric and weight measurements. Ninety-three patients received 166 courses of intravenous antibiotics in full or in part at home during 1991. The average length of treatment was 12.5 days and on average 70% of the treatment was given at home. The mean percentage predicted FEV1 and FVC improved after treatment and the mean improvement was not significantly different to that produced by hospital treatment. Breathlessness, sputum volume, appetite, ability to sleep, mood, energy and overall well-being, as assessed by questionnaire, showed significant improvements after home treatment. The median time spent mixing and administering drugs was 10-19 hours and visiting the hospital was 7-12 hours. The median number of days of lost income to patients or their carers was 0 days. The majority of the patients were extremely satisfied with the treatment and supervision that they received. Using the home care service, 1442 inpatient days were saved. The investigators conclude that home care using 'Intermates' improves a patient's lung function and quality of life.

Extrinsic allergic alveolitis and asthma in a sawmill worker: case report and review of the literature.

A 34 year old sawmill maintenance engineer developed a dry cough that was associated with widespread wheezes and crackles in his lungs. His symptoms worsened, with work related lethargy, fever, and breathlessness, and the loss of a stone in weight. At that time, while still at work, he had a neutrophil leucocytosis and increased concentration of gamma globulins. When seen subsequently some two months after stopping work, his chest radiograph and lung function tests were normal, but the cells recovered at bronchoalveolar lavage showed an increase in lymphocytes and mast cells, a pattern consistent with extrinsic allergic alveolitis. Serum precipitins were identified to extracts of sawdust, wood chips, and bark from the sawmill, and to eight species of mould grown from these samples. Specific IgG binding inhibition studies suggested that a common epitope present on Trichoderma koningii might be responsible for the cross reactivity of the patient's serum with the wood and fungal extracts. A diagnosis of wood associated extrinsic allergic alveolitis was made and since changing his job the patient has remained well. Wood associated allergic alveolitis has not previously been described in British sawmill workers, but has been reported in Sweden, with a prevalence of 5%-10% in exposed workers. A review of published data suggests extrinsic allergic alveolitis in wood workers is primarily caused by inhalation of the spores of contaminating fungi, but inhaled wood dust may exert a synergistic effect.

Respiratory symptoms, immunological responses, and aeroallergen concentrations at a sawmill.

After identification of a case of extrinsic allergic alveolitis due to exposure to wood dust at a sawmill, all employees at the sawmill where he worked were studied with an occupational, environmental, and symptom questionnaire, spirometry, skin prick tests, and serum specific IgG measurements. Ninety five of current and 14 of 17 ex-sawmill workers were studied. As a basis for comparison, a group of 58 workers from a nearby light engineering factory were also studied. Few women (6) were employed and they were excluded from the analysis. Workers at the sawmill were stratified into high and low exposure groups depending on their place of work. This division was supported both by their subjective assessment of the dustiness of their environment and the results of personal dust samples. There were no significant differences between the three groups in age, height, smoking habits, exposure to other causes of extrinsic allergic alveolitis, forced expiratory volume in one second, forced vital capacity, atopic state, or cutaneous reactivity to moulds. In the high exposure group the prevalence of work related cough and nasal and eye symptoms was higher than in the low exposure and comparison groups. The prevalence of work related wheeze was similar in both the high exposure and comparison groups, but was lower in the low exposure group. The prevalences of chronic bronchitis and symptomatic bronchial hyper-reactivity were similar in the high and low exposure groups but were lower in the comparison group. Serum concentrations of specific IgG against extracts of sawdust and Trichoderma koningii were significantly higher in the high exposure group than in the other two groups. The prevalence of symptoms suggestive of extrinsic allergic alveolitis was 4.4% in the high exposure group, greater than in the low exposure group (0%), and the comparison group (1.9%). In conclusion extrinsic allergic alveolitis probably occurs in British sawmills, and among the exposed population its prevalence may be as high as that reported in Sweden. The allergen responsible is likely to be from mould growing on the wood and may be from Trichoderma koningii.