Patient-reported outcome measures in severe asthma: an expert consensus.

OBJECTIVE: The study aimed to reach a consensus on the most relevant patient-reported outcomes (PROs), the corresponding measures (PROMs), and measurement frequency during severe asthma patient follow-up. METHODS: Two Delphi rounds were conducted. The questionnaire was developed based on a systematic literature review, a focus group with patients, and a nominal group with experts. It assessed PROs' relevance and the appropriateness (A) and feasibility (F) of PROMs using a Likert scale (1=totally agree; 9=totally disagree). The consensus was established when ≥75% of participants agreed (1-3) or disagreed (7-9). RESULTS: Sixty-three professionals (25 hospital pharmacists, 14 allergists, 13 pulmonologists, and 11 nurses) and 5 patients answered the Delphi questionnaire. A consensus was reached on all PROs regarding their relevance. Experts agreed on the use of ACT (A:95.24%; F:95.24%), mini AQLQ (A:93.65; F:79.37%), mMRC dyspnea scale (A:85.71%; F:85.71%), TAI (A:92.06%; F:85.71%), MMAS (A:75.40%; F:82%), and the dispensing register (A:96.83%; F:92.06%). Also considered suitable were: SNOT-22 (A:90.48%; F:73.80%), PSQI (A:82.54; F:63.90%), HADS (A:82.54; F:64%), WPAI (A:77.78%; F:49.20%), TSQM-9 (A:79.37; F:70.50%) and knowledge of asthma questionnaire (A:77%; F:68.80%); however, their use in clinical practice was considered unfeasible. Panelists also agreed on the appropriateness of EQ-5D, which was finally included despite being considered unfeasible (A: 84.13%; F:67.20%) in clinical practice. Agreement was reached on using ACT, TAI, mMRC, and a dispensing register every three months; mini-AQLQ and MMAS every six months; and EQ-5D every twelve months. CONCLUSION: This consensus paves the way toward patient-centered care, promoting the development of strategies supporting routine assessment of PROs in severe asthma management.

An atypical location of pineoblastoma RB1 subgroup without pineal or retinal tumor.

PURPOSE: To describe the clinical and imaging features of a sellar-suprasellar pineoblastoma RB1 subgroup without pineal or retinal involvement. CASE REPORT: An 11-month-old girl presented to the emergency department with fever, rhinorrhea, vomiting, altered level of consciousness, and one seizure. Head CT and brain MRI demonstrated a large lobulated mass with calcifications and heterogeneous enhancement in the suprasellar region causing mass effect to the ventricular system and hydrocephalus. Histology revealed a CNS embryonal tumor not otherwise specified (NOS) with small round nuclei with mitotic activity and necrosis. DNA methylation analysis classified the tumor in the pineoblastoma RB1 subgroup. CONCLUSION: Pineoblastoma RB1 subgroup should be considered in the differential diagnosis of large sellar-suprasellar masses with calcifications and heterogeneous enhancement in children younger than 18 months even in cases of absent pineal or retinal involvement. Molecular analysis with DNA methylation profiling is critical for diagnosis and management.

Central nervous system embryonal tumor with PLAGL1 amplification: a case report of a novel entity focusing on imaging findings.

The embryonal central nervous system (CNS) tumor with PLAGL1 (pleomorphic adenoma gene-like) amplification is a novel type of pediatric neoplasm with a distinct methylation profile, described for the first time in 2022. It may be located anywhere in the neuroaxis and, as its name implies, it is driven by the amplification and overexpression of one of the PLAG family genes. Although the associated clinical, immunohistopathological, and molecular characteristics are well characterized in the seminal report of this entity, data on the radiological features is still lacking. Here, we present a case report of a 4-year-old girl with a biopsy-proven PLAGL1-amplified brainstem tumor and provide a detailed description of the corresponding conventional neuroimaging characteristics, aiming to better delineate this entity and to increase the awareness of this pathology in the radiological community.

Achieving clinical outcomes with benralizumab in severe eosinophilic asthma patients in a real-world setting: orbe II study.

BACKGROUND: The ORBE II study aimed to describe the characteristics and clinical outcomes of adult patients with severe eosinophilic asthma (SEA) treated with benralizumab in a real-world setting in Spain. METHODS: ORBE II (NCT04648839) was an observational, retrospective cohort study in adult SEA patients who had been prescribed benralizumab. Demographic and clinical data of 204 SEA patients were collected 12 months prior to benralizumab initiation (baseline) and at follow-up. Exacerbation rate, asthma symptoms, maintenance oral corticosteroid (OCS) use and lung function were evaluated, among other variables. RESULTS: A total of 204 SEA patients were evaluated. Mean (standard deviation, SD) age of the study population was 56.4 (12.4) years, 62.3% were women and mean (SD) duration of asthma was 15.1 (12.7) years. Median (Q1-Q3) follow-up duration was 19.5 (14.2-24.2) months. At baseline, 72.6% of the overall population (OP) presented blood eosinophil counts ≥ 300 cells/µL; 36.8% had comorbid chronic rhinosinusitis with nasal polyps (CRSwNP); 84.8% reported at least one severe exacerbation, and 29.1% were OCS-dependent. At 1 year of follow-up, patients receiving benralizumab treatment had a 85.6% mean reduction in exacerbations from baseline, and 81.4% of patients achieved zero exacerbations. We also found a clinically relevant mean (SD) increase in pre-bronchodilator (BD) FEV1 of 331 (413) mL, with 66.7% of patients achieving a pre-BD FEV1 increase ≥ 100 mL, and 46.3% of patients achieving a pre-BD FEV1 ≥ 80% of predicted. Regarding symptom control, 73.8% of the OP obtained an ACT score ≥ 20 points. After 1 year of follow-up, mean reduction in the daily OCS dose was 70.5%, and complete OCS withdrawal was achieved by 52.8% of the OCS-dependent patients. Almost half (43.7%) of the OP on benralizumab met all four criteria for clinical remission. Patients with concomitant CRSwNP obtained similar or enhanced outcomes. CONCLUSIONS: These data support the real-world benefits of benralizumab in SEA patients, and particularly in those with concomitant CRSwNP. TRIAL REGISTRATION: NCT04648839.

Effects of GLP-1 receptor agonists on neurological complications of diabetes.

Emerging evidence suggests that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) could be an interesting treatment strategy to reduce neurological complications such as stroke, cognitive impairment, and peripheral neuropathy. We performed a systematic review to examine the evidence concerning the effects of GLP-1 RAs on neurological complications of diabetes. The databases used were Pubmed, Scopus and Cochrane. We selected clinical trials which analysed the effect of GLP-1 RAs on stroke, cognitive impairment, and peripheral neuropathy. We found a total of 19 studies: 8 studies include stroke or major cardiovascular events, 7 involve cognitive impairment and 4 include peripheral neuropathy. Semaglutide subcutaneous and dulaglutide reduced stroke cases. Liraglutide, albiglutide, oral semaglutide and efpeglenatide, were not shown to reduce the number of strokes but did reduce major cardiovascular events. Exenatide, dulaglutide and liraglutide improved general cognition but no significant effect on diabetic peripheral neuropathy has been reported with GLP-1 RAs. GLP-1 RAs are promising drugs that seem to be useful in the reduction of some neurological complications of diabetes. However, more studies are needed.

Retinal Neurodegeneration Measured With Optical Coherence Tomography and Neuroimaging in Alzheimer Disease: A Systematic Review.

BACKGROUND: Optical coherence tomography (OCT) has enabled several retinal alterations to be detected in patients with Alzheimer disease (AD), alterations that could be potential biomarkers. However, the relationship between the retina and other biomarkers of AD has been underresearched. We gathered and analyzed the literature about the relationship between retinal and cerebral alterations detected via neuroimaging in patients with AD, mild cognitive impairment (MCI), and preclinical AD. METHODS: This systematic review followed the PRISMA Statement guidelines through the 27 items on its checklist. We searched in PubMed, BVS, Scopus, and the Cochrane Library, using the keywords: Alzheimer's disease, optical coherence tomography, white matter, cortex, atrophy, cortical thickness, neuroimaging, magnetic resonance imaging, and positron emission tomography. We included articles that studied the retina in relation to neuroimaging in patients with AD, MCI, and preclinical AD. We excluded studies without OCT, without neuroimaging, clinical cases, opinion articles, systematic reviews, and animal studies. RESULTS: Of a total of 35 articles found, 23 were finally included. Although mixed results were found, most of these corroborate the relationship between retinal and brain disorders. CONCLUSIONS: More rigorous research is needed in the field, including homogenized, longitudinal, and prolonged follow-up studies, as well as studies that include all stages of AD. This will enable better understanding of the retina and its implications in AD, leading to the discovery of retinal biomarkers that reflect brain alterations in AD patients in an accessible and noninvasive manner.

COVID-19's impact on care practice for alpha-1-antitrypsin deficiency patients.

BACKGROUND: Patients with alpha-1 antitrypsin deficiency (AATD), commonly categorized as a rare disease, have been affected by the changes in healthcare management brought about by COVID-19. This study's aim was to identify the changes that have taken place in AATD patient care as a result of the COVID-19 pandemic in Spain and to propose experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. METHODS: A qualitative descriptive case study with a holistic single-case design was conducted, using focus groups with experts in AATD clinical management, including 15 health professionals with ties to the Spanish health system (12 pneumologists and 2 hospital pharmacists from 11 different hospitals in Spain) and 1 patient representative. RESULTS: COVID-19 has had a major impact on numerous aspects of AATD clinical patient management in Spain, including diagnostic, treatment, and follow-up phases. The experts concluded that there is a need to strengthen coordination between Primary Care and Hospital Care and improve the coordination processes across all the organizations and actors involved in the healthcare system. Regarding telemedicine and telecare, experts have concluded that it is necessary to promote this methodology and to develop protocols and training programs. Experts have recommended developing personalized and precision medicine, and patient participation in decision-making, promoting self-care and patient autonomy to optimize their healthcare and improve their quality of life. The possibility of monitoring and treating AATD patients from home has also been proposed by experts. Another result of the study was the recommendation of the need to ensure that plasma donations are made on a regular basis by a sufficient number of healthy individuals. CONCLUSION: The study advances knowledge by highlighting the challenges faced by health professionals and changes in AATD patient management in the context of the COVID-19 pandemic. It also proposes experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. This work could serve as a reference study for physicians on their daily clinical practice with AATD patients and may also provide guidance on the changes to be put in place for the post-pandemic situation.

Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. METHODS: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 µM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. RESULTS: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). CONCLUSIONS: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www. CLINICALTRIALS: gov (ID: NCT04180319).

Monoclonal antibody treatment for severe uncontrolled asthma in Spain: analytical map.

BACKGROUND: Monoclonal antibodies (mABs) have become available to treat more efficiently patients with severe uncontrolled asthma (SUA). However, the use of mABs is lower than expected given the prevalence of SUA, with significant disparities in the use of these treatments. OBJECTIVE: To evaluate the proportion of patients with SUA treated with mABs in Spain, and to analyze some of the factors that could determine these prescription patterns. METHODS: An analysis was performed on the data provided from the Hospitals National Health System (NHS) 2018 catalogue where Chest Diseases Department and a Hospital Pharmacy were available. Random sampling was performed to determine the sample size, stratifying proportionally by geographic area and hospital level. Characteristics of the participating sites, as well as the prescribing of mABs were collected, which included geographic area, hospital levels, prescribing medical specialities, types of clinics, and mABs prescribed. RESULTS: Data from 90 hospitals were analyzed (Response rate 64.3%). Level 4 hospitals, the Canary Islands geographical area, and the presence of a high complexity Asthma Healthcare Unit (ACU) were associated with a higher probability that the SUA was treated with mABs. CONCLUSION: The map of the prescribing of mABs for SUA in Spain shows a significant variation by geographic area, hospital level, type of clinic, and the accreditation level of the ACUs. At the current time, there appears to be significant under-prescribing of these treatments.

Utility of paramagnetic rim lesions on 1.5-T susceptibility phase imaging for the diagnosis of pediatric multiple sclerosis.

BACKGROUND: Studies have suggested that paramagnetic rim lesions on 7-tesla (T) and 3-T susceptibility-based brain MRI are specific features of multiple sclerosis (MS) lesions in adults. OBJECTIVE: The aim of this study was to investigate whether the presence of paramagnetic rim lesions on 1.5-T phase images can help discriminate pediatric patients with MS from those with other demyelinating diseases. MATERIALS AND METHODS: In this retrospective study we reviewed brain MRIs performed on 1.5-T scanners that included susceptibility-weighted imaging (SWI) sequences with phase images in children younger than 18 years diagnosed with MS and other acquired demyelinating syndromes. In each case, five white matter lesions were selected using T2/fluid-attenuated inversion recovery images for further paramagnetic rim evaluation on SWI. Two researchers performed independent assessments of the presence of paramagnetic rim lesions. Discrepancies between them were settled by consensus, with input from a senior neuroradiologist. RESULTS: We included 13 children diagnosed with MS and 16 children diagnosed with non-MS demyelinating diseases and analyzed a total of 132 focal white matter lesions. Seventy-one percent of the lesions in the MS group had paramagnetic rims, while none of the lesions in the non-MS group had rims. All but one of the children with MS had at least one lesion with a paramagnetic rim. The presence of one lesion with a paramagnetic rim on 1.5-T phase-contrast images resulted in 70% sensitivity and 100% specificity for MS. CONCLUSION: Paramagnetic rim lesions detected on 1.5-T phase-contrast MR images can help discriminate MS from other acquired demyelinating syndromes in the pediatric population.

Craniospinal irradiation as part of re-irradiation for children with recurrent medulloblastoma.

BACKGROUND: Many studies have demonstrated in the last years that once medulloblastoma has recurred, the probability of regaining tumor control is poor despite salvage therapy. Although re-irradiation has an emerging role in other relapsed brain tumors, there is a lack of strong data on re-irradiation for medulloblastoma. METHODS: This is a retrospective cohort study of patients aged 18 years or under, treated at least by a second course of external beam for recurrence medulloblastoma at Garrahan Hospital between 2009 and 2020. Twenty-four patients met eligibility criteria for inclusion. All patients received upfront radiotherapy as part of the curative-intent first radiotherapy, either craniospinal irradiation (CSI) followed by posterior fossa boost in 20 patients or focal posterior fossa radiation in 4 infants. The second course of radiation consisted of CSI in 15 and focal in 9. The 3-year post first failure OS (50% vs. 0%; p = 0.0010) was significantly better for children who received re-CSI compared to children who received focal re-irradiation. Similarly, the 3-year post-re-RT PFS (31% vs. 0%; p = 0.0005) and OS (25% vs. 0%; p = 0.0003) was significantly improved for patients who received re-CSI compared to patients who received focal re-irradiation. No symptomatic intratumoral haemorrhagic events or symptomatic radionecrosis were observed. Survivors fell within mild to moderate intellectual disability range, with a median IQ at last assessment of 58 (range 43-69). CONCLUSIONS: Re-irradiation with CSI is a safe and effective treatment for children with relapsed medulloblastoma; improves disease control and survival compared with focal re-irradiation. However this approach carries a high neurocognitive cost.

Correlation between retinal nerve fibre layer thickness and white matter lesions in Alzheimer's disease.

OBJECTIVES: Early diagnosis in Alzheimer's disease (AD) is crucial in order to implement new therapeutic strategies. The retina is embryologically related to the brain. Thus, the possible usefulness of optical coherence tomography (OCT) in the early detection of AD is currently being studied. Our aim was to study the relationship between retinal nerve fiber layer (RNFL) thickness and AD. METHODS: We undertook an observational, analytical, cross-sectional study with consecutive sampling of 32 patients with AD or mild cognitive impairment and a group of healthy controls (C). The total number of eyes studied was 64. An ophthalmological and a comprehensive neuropsychological evaluation were performed in all participants. Quantification of white matter lesions and study of atrophy of the hippocampus by cerebral magnetic resonance were also performed. RESULTS: We observed a significant linear trend towards a thinning of RNFL as the degree of cognitive deterioration increased, in the superior and temporal quadrants of the retina. A significant correlation was also noted between the mean thickness of the RNFL of the left temporal quadrant and occipital white matter lesions (r = -0.579, p = 0.038). CONCLUSIONS: OCT could be a safe, rapid noninvasive tool providing useful biomarkers in the early detection of cognitive deterioration and AD.

Quantitative characterization of extraocular orbital lesions in children using diffusion-weighted imaging.

BACKGROUND: Diffusion-weighted imaging (DWI) has been shown to be helpful in providing information about cellular density and also predicting the histological features of aggressive tumors. Several studies have evaluated this technique for orbital tumors. However, very few articles have focused exclusively on evaluating pediatric orbital masses and, within those, only a small number of patients were included in the study. OBJECTIVE: This study aimed to evaluate the use of DWI and apparent diffusion coefficient (ADC) values to differentiate between benign and malignant extraocular orbital lesions in children. MATERIALS AND METHODS: This retrospective study included 73 patients under the age of 18 seen in our hospital between October 2016 and February 2019. The extraocular orbital lesions were evaluated clinically and radiologically using DWI. The diagnosis was confirmed by either histological examination (after biopsy or surgery) or based on clinical and radiologic evaluation. RESULTS: The malignant lesions were found to have increased diffusion restriction in comparison to the benign lesions. The ADC values of the malignant lesions were significantly lower (P<0.0001). The use of a cutoff value of 0.99×10-3 mm2/s allowed for the differentiation of the benign lesions and malignant lesions with a sensitivity of 75% and a specificity of 100% while the cutoff point of 1.26×10-3 mm2/s had a sensitivity of 100% and a specificity of 73%. CONCLUSION: Measurement of ADC in extraocular orbital lesions in children may help differentiate malignant lesions from benign lesions.

Treatment of non-obstructive, non-struvite urolithiasis is effective in treatment of recurrent urinary tract infections.

PURPOSE: To determine if treatment of non-obstructing urolithiasis is effective in management of recurrent UTI. MATERIALS AND METHODS: A retrospective review was performed of patients undergoing elective management of non-struvite upper tract urinary calculi with recurrent UTI from 2009 to 2016. Recurrent UTI was defined at ≥ 3 UTI in 12 months, with symptoms and documented urine culture. Preoperative CT was performed in all patients to determine stone burden. All patients had postoperative imaging and ≥ 12 months of follow-up. Pre- and postoperative variables were between patients who had recurrent UTI after treatment versus those who did not. RESULTS: 46 patients met inclusion criteria. 42 (91.3%) were female. Median age was 63.7 years (IQR 49.1, 73.4) and median total stone burden was 20 mm (IQR 14-35). Within the cohort, 20 (43.5%) underwent ureteroscopy only, 26 (56.5%) underwent PCNL ± URS, and none underwent ESWL. Median postoperative follow-up was 2.9 years (IQR 2.0, 4.3). Only five patients (10.9%) had recurrent UTI after treatment. 80% were with the preoperative pathogen. The presence of residual stone was an independent risk factor for recurrent UTI after treatment (p < 0.046). Diabetes, hypertension, immunosuppression and chronic kidney disease were not. CONCLUSIONS: Stone removal for patients with recurrent UTIs was associated with a high rate of success (89.1%) in elimination of further recurrent UTIs. Residual fragments are independently associated with persistent recurrent UTIs and thus, complete stone removal is of paramount importance in treatment of this patient population.

Introduction of HPV testing for cervical cancer screening in Central America: The Scale-Up project.

The Scale-Up project introduced vaginal self-sampling and low-cost human papillomavirus (HPV) testing as the primary approach for cervical cancer screening in selected public health centers in Guatemala, Honduras, and Nicaragua. We evaluate the country-specific accomplishments in screening: target-coverage, triage, and treatment. Between 2015 and 2018, cervical cancer screening was offered to women at least 30 years of age. Triage of HPV-positive women was based on visual inspection with acetic acid or Pap. Aggregated data included total women screened, use of self-sampling, age, time elapsed since last screening, HPV results, triage tests, triage results, and treatment. A total of 231,741 women were screened for HPV, representing 85.8% of the target populations within the project. HPV positivity was lower in Guatemala (12.4%) compared to Honduras and Nicaragua (14.5% and 14.2%, respectively, p < 0.05). A follow-up triage test was completed for 84.2%, 85.8%, and 50.1% of HPV-positive women in Guatemala, Nicaragua, and Honduras, respectively. Of those with a positive triage test, 84.7%, 67.1%, and 58.8% were treated in Guatemala, Nicaragua, and Honduras, respectively. First-time screening was highest in Nicaragua (55.8%) where self-sampling was also widely used (97.1%). The Scale-Up project demonstrated that large-scale cervical cancer screening and treatment intervention in a high-burden, low-resource setting can be achieved. Self-sampling and ablative treatment were key to the project's achievements. Data monitoring, loss to follow-up, and triage methods of screen- positive women remain critical to full success.

HPV-based cervical cancer screening in Nicaragua: from testing to treatment.

BACKGROUND: In Nicaragua, cervical cancer is the leading cause of cancer death among women. Human papillomavirus (HPV) testing, primarily using self-sampling, was introduced between 2014 and 2018 in three provinces. We analyzed data from the HPV screening program with the goal of describing key characteristics including reach, HPV prevalence, triage and treatment, and factors associated with follow-up completion. METHODS: We analyzed individual-level data from routinely collected forms for women attending HPV-based cervical cancer screening. HPV-positive women were triaged with Pap or visual inspection with acetic acid (VIA) prior to treatment. Logistic regression was used to identify factors associated with receiving triage and treatment; analyses were adjusted for province, age, and self- vs. provider-collected sampling. RESULTS: Forty-four thousand six hundred thirty-five women were screened with HPV testing; 96.6% of women used self-sampling. Six thousand seven hundred seventy-six women were HPV positive (15.2%), 54.0% of screen-positive women received triage, and 53.1% of triage-positive women were treated, primarily with cryotherapy. If women lost at triage are included, the overall treatment percentage was 27.8%. Province and provider sampling were significantly associated with completing triage. Province and triage type were significantly associated with receiving treatment. The odds of receiving treatment after Pap triage as compared to VIA was significantly lower (aOR: 0.05, 95% CI: 0.04-0.08, p < 0.001), and the relative proportion of women receiving treatment after Pap triage versus VIA was 0.29. CONCLUSIONS: Introduction of HPV testing resulted in a substantial number of women screened, and acceptance of self-sampling was high. Management of screen-positive women remained a challenge, particularly with Pap triage. Our results can inform other developing countries as they work to reach World Health Organization (WHO) elimination targets.

The Importance of Reference Centers and Registries for Rare Diseases: The Example of Alpha-1 Antitrypsin Deficiency.

Alpha-1 antitrypsin deficiency (AATD) is a rare and underdiagnosed disease that is associated with the development of liver disease in adults and children and pulmonary emphysema in adults. Several studies have shown that there is limited knowledge about the disease and its diagnosis among health care providers, and there is an important inequity in the access to specialized care and appropriate treatment across Europe. The European Commision and the European Respiratory Society (ERS) recommend that the care of patients with AATD must be organized in reference centers at national or regional levels. These reference centers must provide optimal clinical care in terms of adequate diagnostic techniques, such as phenotyping and genotyping, and ensure access to treatment according to guidelines. Reference centers should also provide continuous medical education for health care professionals, genetic counseling, collaboration with patient associations and promote collaborative research and clinical trials with new and existing treatments for the disease. These centers must have a registry of their activity and collaborate with large, international, multicenter registries, such as the European Alpha-1 antitrypsin Deficiency Research Collaboration (EARCO) international registry, which is endorsed by the ERS, and aims to recruit up to 3,000 patients over a period of three years and prospectively follow them to better understand the natural history of the disease and the impact of different treatments on outcomes in a real life setting. International collaboration and standardized collection of high-quality prospective data will provide new insights into the clinical manifestations and prognosis of AATD.

Geographical Distribution of COPD Prevalence in the Americas.

Surveys estimating chronic obstructive pulmonary disease (COPD) prevalence are unevenly distributed in the Americas, which make it difficult to estimate accurately its geographical distribution. The geographic information system inverse distance weighted (IDW) interpolation technique has proved to be an effective tool in spatial distribution estimation of epidemiological variables, even when real data are few or widely spread. We aimed to represent cartographically the COPD prevalence in the Americas by means of a blue to red scale representation of the prevalence data, where different values are represented as different colours, and a population density filtered IDW interpolation mapping, where areas with a population density <0.1 inhabitants/km2 are hidden. We systematically searched for prevalence rates from population surveys of individuals 40 years and older, and a COPD diagnosis confirmed by spirometry. Interpolation maps were obtained for the whole Americas, even from extensive areas lacking real data. Maps showed high prevalence values in the Southeast and Southwest regions of Canada bordering the United States; in several states of the Great Lakes region, and in the lower Missouri, Ohio and Mississippi basins of the United States; in the coastal regions of south-eastern and southern Brazil; Uruguay, and the Argentine Pampas. In general, most of the remaining American regions showed intermediate values of COPD prevalence. IDW interpolation seems to be a suitable tool to visually display estimates of COPD prevalence, and it may be a valuable help to draw attention about the worrying prevalence of this preventable and treatable disease.