Cardiovascular disease in Alpha 1 antitrypsin deficiency: an observational study assessing the role of neutrophil proteinase activity and the suitability of validated screening tools.

BACKGROUND: Alpha 1 Antitrypsin Deficiency (AATD) is a rare, inherited lung disease which shares features with Chronic Obstructive Pulmonary Disease (COPD) but has a greater burden of proteinase related tissue damage. These proteinases are associated with cardiovascular disease (CVD) in the general population. It is unclear whether patients with AATD have a greater risk of CVD compared to usual COPD, how best to screen for this, and whether neutrophil proteinases are implicated in AATD-associated CVD. This study had three aims. To compare CVD risk in never-augmented AATD patients to non-AATD COPD and healthy controls (HC). To assess relationships between CVD risk and lung physiology. To determine if neutrophil proteinase activity was associated with CVD risk in AATD. Cardiovascular risk was assessed by QRISK2® score and aortic stiffness measurements using carotid-femoral (aortic) pulse wave velocity (aPWV). Medical history, computed tomography scans and post-bronchodilator lung function parameters were reviewed. Systemic proteinase 3 activity was measured. Patients were followed for 4 years, to assess CVD development. RESULTS: 228 patients with AATD, 50 with non-AATD COPD and 51 healthy controls were recruited. In all COPD and HC participants, QRISK2® and aPWV gave concordant results (with both measures either high or in the normal range). This was not the case in AATD. Once aPWV was adjusted for age and smoking history, aPWV was highest and QRISK2® lowest in AATD patients compared to the COPD or HC participants. Higher aPWV was associated with impairments in lung physiology, the presence of emphysema on CT scan and proteinase 3 activity following adjustment for age, smoking status and traditional CVD risk factors (using QRISK2® scores) in AATD. There were no such relationships with QRISK2® in AATD. AATD patients with confirmed CVD at four-year follow up had a higher aPWV but not QRISK2® at baseline assessment. CONCLUSION: aPWV measured CVD risk is elevated in AATD. This risk is not captured by QRISK2®. There is a relationship between aPWV, lung disease and proteinase-3 activity. Proteinase-driven breakdown of elastin fibres in large arteries and lungs is a putative mechanism and forms a potential therapeutic target for CVD in AATD.

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.

"We can't carry the weight of the whole world": illness experiences among Peruvian older adults with symptoms of depression and anxiety.

BACKGROUND: Despite the high levels of depression and anxiety symptoms in old age, the use of mental health services in this population is low. Help-seeking behaviors are shaped by how an individual perceives and experiences their illness. The objective of this study was to characterize the illness experiences of Peruvian older adults with depression and anxiety symptoms in order to lay the foundation for tailored community-based mental health interventions. METHODS: In this qualitative study, we conducted in-depth interviews with a purposively selected sample of older adults (≥ 60 years) from peri-urban areas of Lima, Peru. We included individuals with only depressive symptoms (Patient Health Questionnaire-9 ≥ 10), only anxiety symptoms (Beck Anxiety Inventory ≥ 16), with depressive and anxiety symptoms, and older adults who mentioned they had received mental health treatment/care. The interview guide included the following topics: perceptions and experiences about depression and anxiety; perceptions about the relationship between physical chronic diseases and mental health; experiences with mental health professionals and treatments, and coping mechanisms. Data collection was conducted between October 2018 and February 2019. RESULTS: We interviewed 38 participants (23 women, 15 men) with a mean age of 67.9 years. Participants' ideas and perceptions of depression and anxiety showed considerable overlap. Participants attributed depression and anxiety mainly to familial and financial problems, loneliness, loss of independence and past traumatic experiences. Coping strategies used by older adults included 'self-reflection and adaptation' to circumstances, 'do your part', and seeking 'emotional support' mainly from non-professionals (relatives, friends, acquaintances, and religion). CONCLUSIONS: Illness experiences of depression and anxiety set the pathway for tailored community-based mental health interventions for older adults. Overlapping narratives and perceptions of depression and anxiety suggest that these conditions should be addressed together. Mental health interventions should incorporate addressing areas related to depression and anxiety such as prevention of loss of independence, trauma, and loneliness. Good acceptability of receiving emotional support for non-professionals might offer an opportunity to incorporate them when delivering mental health care to older adults.

Pollution and respiratory disease: can diet or supplements help? A review.

Pollution is known to cause and exacerbate a number of chronic respiratory diseases. The World Health Organisation has placed air pollution as the world's largest environmental health risk factor. There has been recent publicity about the role for diet and anti-oxidants in mitigating the effects of pollution, and this review assesses the evidence for alterations in diet, including vitamin supplementation in abrogating the effects of pollution on asthma and other chronic respiratory diseases. We found evidence to suggest that carotenoids, vitamin D and vitamin E help protect against pollution damage which can trigger asthma, COPD and lung cancer initiation. Vitamin C, curcumin, choline and omega-3 fatty acids may also play a role. The Mediterranean diet appears to be of benefit in patients with airways disease and there appears to be a beneficial effect in smokers however there is no direct evidence regarding protecting against air pollution. More studies investigating the effects of nutrition on rapidly rising air pollution are urgently required. However it is very difficult to design such studies due to the confounding factors of diet, obesity, co-morbid illness, medication and environmental exposure.

Prevalence and risk factors of restrictive spirometry in a cohort of Peruvian adults.

INTRODUCTION: Few studies have described the prevalence of and lung function decline among those with a restrictive spirometric pattern (RSP) in low- and middle-income countries. METHODS: We analyzed prospective data from 3055 adults recruited across four diverse settings in Peru over a 3-year period. Multivariable logistic regression was used to study the association between the presence of restriction and associated risk factors. Multivariable linear mixed models were used to determine lung function decline. RESULTS: Among 3055 participants, the average age was 55.4 years (SD 12.4); 49% were male. Overall prevalence of RSP was 4.7%, ranging from 2.8% (Lima) to 6.9% (Tumbes). The odds of having RSP were higher among those who lived in a rural environment (OR 2.19, 95%CI 1.43-3.37), had a diagnosis of diabetes (OR 1.94, 95%CI 1.10-3.40) and among women (OR 2.09, 95%CI 1.41-3.09). When adjusting for baseline lung function, adults with RSP had accelerated decline in forced expiratory volume in 1 s (FEV1) compared with non-obstructed, non-restricted individuals. DISCUSSION: RSP is prevalent particularly among women and in individuals living in rural settings of Peru. When adjusted for baseline lung function, participants with RSP had accelerated rates of FEV1 decline. Our findings are consistent with the notion that RSP is an insidious inflammatory condition with deleterious effects of lung function decline.

Viruses and exacerbations of chronic obstructive pulmonary disease: unmet clinical need.

Chronic obstructive pulmonary disease (COPD) is a non-communicable long-term condition characterised by accelerated lung-function decline and intermittent episodes of respiratory illness called exacerbations. We discuss the current understanding of the role of viruses in these elements of COPD. The burden of acute viral illness in COPD is great and largely unrecognised. Because naturally occurring exacerbations are inherently difficult to study, only recently have we understood underlying pathophysiological mechanisms and the true prevalence of viral exacerbations. Data are also emerging to support a potential role for chronic viral infection in the progression of stable COPD. As knowledge in these two areas develops, it is clear that the role of viruses in COPD represents a significant unmet clinical need.

Predictive accuracy of patient-reported exacerbation frequency in COPD.

Chronic obstructive pulmonary disease (COPD) exacerbation frequency is important for clinical risk assessment and trial recruitment. In order to accurately establish exacerbation frequency, patients need to be followed for 1 yr, although this is not always practical. 1) Patient recall of exacerbation number during the year prior to recruitment to the London COPD cohort was compared with the number of exacerbations recorded on diary cards during the subsequent year; and 2) patient recall of their exacerbation number after 1 yr of follow-up was compared with documented exacerbations over the same year. A total of 267 patients (forced expiratory volume in 1 s 1.14 L) recorded worsening of respiratory symptoms on daily diary cards for 1 yr. Exacerbations were defined according to previously validated criteria. There was no difference between the exacerbation number recalled by patients prior to recruitment and the number detected during the first year (median 2.0 (interquartile range 1.0-4.0) and 2.0 (1.0-4.0); expected agreement 76.4%; agreement 84.6%; κ = 0.3469). There was no difference between the number of exacerbations remembered by patients and the number recorded on diary cards over the same 1-yr period (2.0 (1.0-4.0) for both groups; expected agreement 74.9%; actual agreement 93.3%; κ = 0.6146). Patients remember the number of exacerbations they have in a year. Accuracy is increased when comparing the same 1-yr period. Patient recall is sufficiently robust for stratification into frequent and infrequent exacerbator groups for subsequent years.

Upper airway. 3: Sinonasal involvement in chronic obstructive pulmonary disease.

This review presents the evidence that chronic obstructive pulmonary disease (COPD) is associated with significant sinonasal symptoms, inflammation and airway obstruction. Upper airway symptoms in COPD cause impairment to quality of life. The severity of upper airway involvement relates to that present in the lower airway, suggesting that the nose may be used to model the lung in COPD. More importantly, relationships between upper and lower airway bacteria and inflammation, and the association between sinusitis and treatment failure at exacerbation raise the possibility that nasal intervention in COPD may not only improve health status but may also affect important clinical outcomes such as exacerbation frequency.

UK national survey of current practice and experience of intravitreal triamcinolone acetonide.

AIMS: In recent years, intravitreal triamcinolone acetonide (IVTA) injections have become widely used in the treatment of macular oedema. IVTA can cause elevation of intraocular pressure (IOP), which can be sight threatening. We carried out a nationwide study, which aimed to (i) assess the current usage of IVTA, (ii) estimate the incidence of 'severe' IOP rise following IVTA, in routine practice. METHODS: A postal survey was carried out in January 2007. A questionnaire was mailed to senior ophthalmologists (all consultants and associate specialists) in the United Kingdom. We asked about the use of IVTA over the past year and whether there had been any cases of severe IOP rise (defined as elevation in IOP, commencing after IVTA therapy, requiring laser or surgery to treat the raised pressure). RESULTS: Response rate was 56% (611/1089). Among respondents, 33% (206) had used IVTA during the 12 months of 2006 giving a total of 3899 IVTA injections. There were 45 reported cases of severe IOP rise, following IVTA injections, which were given under their care of the respondent. A further 28 cases were reported to have been referred from colleagues; it is unclear whether any or all of these cases were included in the initial 45. The reported rate of severe IOP rise following IVTA was therefore at least 45/3899 or at least 1.1%. CONCLUSIONS: Usage of IVTA in the United Kingdom is widespread. Severe IOP rise, requiring laser or surgery to control IOP, was reported in at least 1.1% of cases.

Purpura fulminans associated with Lactobacillus paracasei liver abscess.

Purpura fulminans is a rare but devastating haemorrhagic condition often associated with sepsis. Many different organisms have been implicated in the aetiology of purpura fulminans, most commonly Neisseria meningitidis and Streptococcus pneumoniae. We report a case of purpura fulminans associated with Lactobacillus paracasei liver abscess. Purpura fulminans has not previously been associated with this organism and specific bacteriological testing was used to exclude the presence of other species.

Inflammatory changes, recovery and recurrence at COPD exacerbation.

Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased airway and systemic inflammation, though relationships between exacerbation recovery, recurrent exacerbation and inflammation have not been previously reported. In the present study, inflammatory changes at COPD exacerbations were related to clinical nonrecovery and recurrent exacerbations within 50 days. Serum interleukin (IL)-6, C-reactive protein (CRP), sputum IL-6 and IL-8 were measured in 73 COPD patients when stable, at exacerbation and at 7, 14 and 35 days post-exacerbation. In 23% of patients, symptoms did not recover to baseline by day 35. These patients had persistently higher levels of serum CRP during the recovery period. A total of 22% of the patients who had recurrent exacerbations within 50 days had significantly higher levels of serum CRP at day 14, compared with those without recurrences: 8.8 mg.L(-1) versus 3.4 mg.L(-1). Frequent exacerbators had a smaller reduction in systemic inflammation between exacerbation onset and day 35 compared with infrequent exacerbators. Nonrecovery of symptoms at chronic obstructive pulmonary disease exacerbation is associated with persistently heightened systemic inflammation. The time course of systemic inflammation following exacerbation is different between frequent and infrequent exacerbators. A high serum C-reactive protein concentration 14 days after an index exacerbation may be used as a predictor of recurrent exacerbations within 50 days.

Epidemiological relationships between the common cold and exacerbation frequency in COPD.

Higher exacerbation incidence rates in chronic obstructive pulmonary disease (COPD) are associated with more rapid decline in lung function and poorer quality of life, yet the mechanisms determining susceptibility to exacerbation remain ill-defined. The same viruses responsible for common colds are frequently isolated during exacerbations. The current authors hypothesised that exacerbation frequency may be associated with an increased frequency of colds, and investigated whether increased exacerbation frequency was associated with increased acquisition of colds, or a greater likelihood of exacerbation once a cold has been acquired. A total of 150 patients with COPD completed diary cards recording peak expiratory flow, and respiratory and coryzal symptoms for a median 1,047 days. Annual cold and exacerbation incidence rates (cold and exacerbation frequency) were calculated, and the relationships between these variables were investigated. This analysis is based on 1,005 colds and 1,493 exacerbations. Frequent exacerbators (i.e. those whose exacerbation frequency was greater than the median) experienced significantly more colds than infrequent exacerbators (1.73 versus 0.94.yr(-1)). The likelihood of exacerbation during a cold was unaffected by exacerbation frequency. Patients experiencing frequent colds had a significantly higher exposure to cigarette smoke (46 versus 33 pack-yrs). Exacerbation frequency in chronic obstructive pulmonary disease is associated with an increased frequency of acquiring the common cold, rather than an increased propensity to exacerbation once a cold has been acquired.

Chronic obstructive pulmonary disease: the clinical management of an acute exacerbation.

Exacerbations of chronic obstructive pulmonary disease impose a considerable burden of morbidity, mortality, and health care cost. Management guidelines outlining best practice, based largely on consensus expert opinion, were produced by a number of organisations during the last decade. Current interest in the field is high. This has resulted in the publication of many further studies which have extended our understanding of the pathology involved and provided, for the first time, an evidence base for many of the therapeutic options. In this review we aim to bring the non-specialist reader up to date with current management principles and the evidence underlying such interventions.