Impact of Coronavirus Disease 2019 and Vaccination Attitudes on Alpha-1 Antitrypsin Deficiency.

The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Lung and Heart–Lung Transplant Report—2016; Focus Theme: Primary Diagnostic Indications for Transplant

Rationale: Alpha-1 antitrypsin deficiency (AATD), an under-recognized genetic condition, can cause chronic obstructive pulmonary disease (COPD) and/or liver disease in adults. Symptoms of individuals who have COPD and/or liver disease due to AATD are often indistinguishable from those without deficiency, necessitating additional tools to establish diagnosis. Using claims data from the large United States Komodo Health database, we previously reported an artificial intelligence model to identify symptomatic patients who likely had AATD but were unrecognized. In this current study, we used retrospective deidentified patient data generated from the Cleveland Clinic Electronic Medical Record (EMR) to define and characterize patient cohorts utilized to calibrate and refine the model. Methods: Data from deidentified patient records, sourced from the Cleveland Clinic EMR between January 1, 1998 and August 15, 2024, were analyzed. Patients who had positive AATD diagnoses were grouped into categories depending upon how diagnoses were confirmed (genetic: genotype confirming AATD; severe: severe deficiency in AAT serum levels [<57 mg/dL]; and mild: mild deficiency in AAT serum levels [57-90 mg/dL]). Clinical phenotype and treatment patterns for these subgroups were analyzed based on the presence of relevant medical codes in patients’ records. Results: Of 794 patients with AATD, 290 patients (36.5%) were identified by genotype (genetic), the remaining patients were characterized by serum AAT level in the severe (n=117, 14.7%) and mild (n=387, 48.7%) categories. Overall, 50.4% of patients were male; median age was 63 years. Prevalence of common comorbidities was lower in the mild subgroup versus the total population and other subgroups: COPD (total: 40.1%, genetic: 44.8%, severe: 47.9%, mild: 34.1%), unspecified liver disease (total: 34.9%, genetic: 41.4%, severe: 40.2%, mild: 28.4%), and emphysema (total: 31.7%, genetic: 36.9%, severe: 38.5%, mild: 25.8%). Overall, 12.5% of patients had any AATD augmentation therapy drug in their records. When assessed by subgroup, 22.4% of the genetic group, 17.9% of the severe group, and 3.4% of the mild group had an augmentation therapy drug listed in their records; patients with emphysema had higher rates of receiving augmentation therapy than patients without (Figure 1). Conclusions: Within the Cleveland Clinic EMR, this analysis identified phenotypic and treatment pattern differences among cohorts of patients confirmed to have AATD. Lower frequencies of comorbidities, as well as lower rates of patients who received augmentation therapy for AATD, were observed in patients with mild deficiency of AAT compared with patients with confirmed genetic diagnoses and those with severe deficiency of AAT.

BackgroundCirculating free light chains (FLCs) can alter neutrophil migration, apoptosis and activation and may be a biomarker of autoimmune disease and adaptive immune system activation. These pathogenic roles could be relevant to lung disease in alpha 1 antitrypsin deficiency (A1ATD) and chronic obstructive pulmonary disease (COPD).MethodsTotal combined (c)FLCs were measured using the FreeLite® assay in 547 patients with A1ATD and 327 patients with usual COPD in the stable state, and assessed for association with clinical phenotype, disease severity, airway bacterial colonisation and mortality. Univariate and multivariate analyses were undertaken.ResultsCirculating cFLCs were static in the stable state when measured on 4 occasions in A1ATD and twice in usual COPD. Levels were inversely related to renal function (A1ATD and COPD p = <0.01), and higher in patients with chronic bronchitis (p = 0.019) and airway bacterial colonisation (p = 0.008). After adjusting for renal function and age the relationship between cFLCs and lung function was weak. Kaplan Meier curves showed that cFLC > normal (43.3 mg/L) significantly associated with mortality in both cohorts (A1ATD p = 0.001, COPD p = 0.013).ConclusionscFLCs may be a promising biomarker for risk stratification in A1ATD and COPD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0348-1) contains supplementary material, which is available to authorized users.

Unique and shared systemic biomarkers for emphysema in Alpha-1 Antitrypsin deficiency and chronic obstructive pulmonary disease.

Persons with cancer are at increased risk of severe COVID-19 infection, but the additional benefit of COVID-19 boosters is unclear. To assess COVID-19 vaccine effectiveness (VE) and number needed to vaccinate (NNV) among persons with cancer of an additional dose of the monovalent COVID-19 vaccine. Retrospective cohort study conducted in 4 health care systems in the US among persons with cancer receiving chemotherapy or immunotherapy. Statistical analysis was conducted between March 2023 and August 2024. Receipt of an additional dose of the monovalent COVID-19 vaccine before January 1, 2022, with follow-up until August 31, 2022, and the bivalent COVID-19 vaccine from September 1, 2022, to August 31, 2023. COVID-19 hospitalization, diagnosed COVID-19, and COVID-19-related intensive care unit (ICU) admission. Among 72 831 persons with cancer (17 922 female individuals [24.6%]), 69% received a monovalent booster by January 1, 2022. During 34 006 person-years of follow-up, the COVID-19 hospitalization rate was 30.5 per 1000 person-years among patients who received a monovalent booster vs 41.9 per 1000 person-years among patients who received the primary series alone, with an adjusted VE of 29.2% (95% CI, 19.9%-37.3%) and NNV to prevent 1 COVID-19 hospitalization of 166 (95% CI, 130-244). There was also significant VE to prevent diagnosed COVID-19 (8.5% [95% CI, 3.7%-13.0%]) and COVID-19-related ICU admission (35.6% [95% CI, 20.0%-48.3%]). Among 88 417 persons with cancer (24 589 female individuals [27.8%]) with 81 027 person-years of follow-up during the bivalent period, patients who received this booster (38%) had a COVID-19 hospitalization rate of 13.4 per 1000 person-years vs 21.7 per 1000 person-years among persons who did not receive a bivalent vaccine, with an adjusted VE of 29.9% (95% CI, 19.4%-39.1%) and NNV to prevent 1 COVID-19 hospitalization of 451 (95% CI, 345-697); the adjusted VE was 30.1% (95% CI, 7.7%-47.0%) to prevent COVID-19-related ICU admission. In this retrospective cohort study, COVID-19 booster vaccinations were associated with significant protection against severe COVID-19, with a favorable NNV among persons with cancer. However, uptake of COVID-19 vaccine boosters was low, and interventions are therefore justified to increase COVID-19 uptake in this high-risk population.

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by a highly infectious respiratory virus (SARS-CoV-2). With all these consequences that threaten the health of the individual and society due to this infection, it has become necessary to have a vaccination that limits the spread of this virus. The objective of this study was to study the epidemiological aspects of COVID-19 pandemic in Jeddah, Saudi Arabia. Method: It was a cross sectional study of 405 subjects, who gave their responses through online Google form, as face to face interview of the subjects during outpatient clinic visits was not possible because of the pandemic of COVID-19 infection. Data was analyzed using SPSS software version 23. The level of significance was 0.05%. Results: The prevalence of Covid-19 infection was 23.7%. The vaccination coverage by the Covid-19 vaccine was 90.4%. Those who got the infection before getting the vaccine were 76%; on the other hand those who got the infection after getting one dose were 17.7% of the cases, while 6.3% got the infection after getting two doses of the vaccine. Those with autoimmune disorders, kidney failure and obesity were reluctant to get the vaccine (p &lt;0.05). Married subjects, those with average income, and those who are employed were significantly more infected by COVID-19 (p&lt;0.05). Patients with asthma, with autoimmune disorders,and those who did not take the COVID-19 vaccine, were significantly more vulnerable to COVID – 19 infection (p&lt;0.05). Post vaccination clinical manifestations were mainly feeling tired (90.2%), pain and swelling at the site of injection (76.9%), fever (65.9%) and headache (61.8%%). Clinical manifestations associated with COVID-19 infection included fever (76.0%), headache (72.9%), loss of taste and smell (68.8%), body aches (67.7%), and sore throat (57.3%). Conclusions: Prevalence of COVID-19 infection was 23.7%. About one third of the population did not accept the vaccine. Subjects with asthma, autoimmune disorders, and those who were unvaccinated were more likely to catch the infection. Increasing the knowledge of the people about the clinical aspects, and health impact of the COVID-19 virus on the community are important intervention tools to increase the acceptance rate of COVID-19 vaccination among the population. Key words: COVI-19, clinical aspects and acceptance of COVID-19 infection.

Evidence-based guidelines recommend screening all individuals with chronic obstructive pulmonary disease (COPD) for the genetic disorder alpha-1 antitrypsin deficiency (AATD). However, it is estimated that only 5% of people with COPD have been tested for AATD, and a large fraction of the estimated 70,000 to 100,000 Americans with AATD have not yet been diagnosed. Low familiarity with AATD and limited knowledge about diagnostic tests and available treatments contribute to suboptimal screening rates. Our objective was to address barriers to and improve rates of guideline-based AATD diagnostic testing among racially and ethnically diverse patients with COPD at a large community health center. A quality improvement initiative consisting of educational sessions and electronic health record (EHR) system interventions was implemented to improve the adoption of guideline-based screening for AATD in patients with COPD. An analysis of EHR data demonstrated that among patients with a COPD diagnosis (n=1030), 22.2% (n=229) were screened for AATD in the 12 months following the start of the quality improvement initiative compared with 1.3% (n=13) of patients with a COPD diagnosis (n=972) seen in the 12 months prior to the start of the quality improvement initiative (P<0.001). A quality improvement initiative consisting of educational sessions and EHR system modifications was successful in increasing clinicians' knowledge and diagnostic screening rates for AATD in patients with COPD at a large community health center.

Alpha1-antitrypsin (AAT) deficiency is a recognized susceptible factor for chronic obstructive pulmonary disease (COPD) in Western countries, but its importance in Korea is unclear. To date, no definitive case of alpha1-antitrypsin deficiency has been reported in Korea. This study aimed to clarify whether alpha1-antitrypsin deficiency exists and to determine the distribution of alpha1-antitrypsin alleles in the Korean population. The serum concentrations of alpha1-antitrypsin were determined and polymorphisms of the alpha1-antitrypsin gene in 114 COPD patients and in 196 healthy controls were examined. Phenotyping by isoelectric focusing and the genotyping of alpha1-antitrypsin gene by polymerase chain reaction and restriction fragment length polymorphism were performed. No alpha1-antitrypsin level abnormality was found in the patients. M1(Val)/M1(Val) was found to be the most frequent genotype in both groups (69.2% and 66.8%, respectively), and M1(Val) the most frequent allele. The distributions of alpha1-antitrypsin alleles were similar in the patient and control groups, and no S or Z allele was found. Alpha1-antitrypsin deficiency is unlikely to be an important cause of chronic obstructive pulmonary disease in the Korean population.

BackgroundTrials of disease modifying therapies in Chronic Obstructive Pulmonary Disease (COPD) provide challenges for detecting physiological and patient centred outcomes. The purpose of the current study was to monitor decline in health status in Alpha-1 antitrypsin deficiency (AATD) and determine its’ relationship to conventional physiology.MethodsPatients recruited to the UK-AATD database with a median follow up of 7 years (IQR 5–10) were studied to determine annual change in St George’s Respiratory Questionnaire (SGRQ), FEV1, gas transfer and their feasibility of use in future trials.ResultsAnnual decline in SGRQ had a wide range, was greater for patients with established COPD and correlated with decline in FEV1 (p < 0.0001). Total score decline was greater (p < 0.05) for those with accelerated FEV1 decline (median = 1.07 points/year) compared to those without (median = 0.51). Power calculations indicated effective intervention would not achieve MCID for the SGRQ unless the timeframe was extended for up to 8 years. More than 5000 patients/arm would be required for a statistically significant modest effect over 3 years even in those with rapid FEV1 decline.ConclusionDespite AATD being a rapidly declining form of COPD, deterioration in SGRQ was slow consistent with ageing and the chronic nature of disease progression. Power calculations indicate the numbers needed to detect a difference with disease modifying therapies would be prohibitive especially in this rare cause of COPD. These data have important implications for future study design of disease modifying therapies even in COPD not associated with AATD.

Background: Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed condition despite being one of the most common inherited disorders in adults that is associated with an increased risk of developing chronic obstructive pulmonary disease (COPD). The aim was to evaluate the frequency of performing AAT levels and associated factors in COPD patients in an audit conducted in 2021–2022, as well as to compare with a previous audit conducted in 2014–2015. Methods: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to COPD patients in respiratory clinics in Spain based on available data from medical registries. Results: 4225 patients with a diagnosis of COPD from 45 centers were audited in 2021. A total of 1670 (39.5%) patients underwent AAT determination. Being treated at a specialized COPD outpatient clinic (OR 1.88, p = 0.007), age ≤ 55 years old (OR 1.84, p = 0.007) and a FEV1 < 50% (OR 1.86, p < 0.001) were associated with a higher likelihood of being tested for AAT, while Charlson index ≥ 3 (OR 0.63, p < 0.001) and genotyping of AATD availability (OR 0.42, p < 0.001) showed a statistically significant negative association. The analysis of cases included in respiratory units that participated in both audits showed an increase in the proportion of cases with AAT serum level testing available (adjusted OR 2.81, p < 0.001). The percentage of individuals with serum AAT levels < 60 mg/dL (a severe AATD) was 4%. Conclusions: Our analysis identifies significant improvements in adherence to the recommendation to test AAT levels in COPD patients, performed in 4 out of 10 patients, being more likely at younger ages and with higher COPD severity, and with a detection of severe AATD of 4% among those tested, suggesting that clinicians still perform AAT testing in COPD patients selectively. Therefore, efforts are still needed to optimize AATD screening and establish new early detection strategies to reduce morbidity and mortality in these patients.

Alpha 1-antitrypsin deficiency is a genetic risk factor for manifestation of COPD and chronic liver diseases. There is an ongoing worldwide discussion concerning the role of serpins (serine protease inhibitors) in tumour genesis. Protease inhibitors such as alpha 1-antitrypsin have generally been considered to counteract tumour progression and metastases because of their ability to inhibit proteases. In this case report, we ana-lyze relationship between inherited alpha-1 antitrypsin deficiency and chondrosarco-chondrosarcoma. The patient had also a history of COPD. After chest X-ray and CT, alpha 1-antitrypsin deficiency was suspected. Inherited alpha-1 antitrypsin deficiency (PiZZ homozygous genotype) was confirmed. Alpha 1-antitrypsin deficiency might have facilitated the development of chondrosarcoma. Because of low incidence rate of such diseases, we presume that there is a slight chance for such rare disorders to manifest concurrently in the same patient.Key words: alpha 1-antitrypsin deficiency, chondrosarcomaabbreviations: COPD – chronic obstructive pulmonary disease; serpins – serine pro-tease inhibitors; CT – computed tomography.

Background: The Corona Virus (SARS-COV2) is one of the major pathogens that affect the human respiratory system. As it spreads via droplets, healthcare workers are at increased risk of acquiring the infection. Nursing students who are exposed to the hospital setting during their clinical postings are prone to infection because they may provide care to patients who are suspected of or diagnosed with COVID-19 infection. In dentistry, the use of hand pieces and ultrasonic instruments during dental procedures unavoidably result in generation of blood and saliva droplets. Objective was to estimate the prevalence of COVID-19 infection among Dental and Nursing students of Government dental college and nursing college, Alappuzha. Methods: A cross sectional study was conducted in Dental and Nursing students of Government TD Dental College and Nursing College, Alappuzha in November 2021. Convenient sampling was done and persons who were willing to take part in the study were distributed with a pretested questionnaire via Google Form and data was collected and analysed. Results: Out of the 174 study participants, 77 were Dental students and 97 were Nursing students, 33% of Dental students and 36% of Nursing students reported of being infected with COVID-19 virus. Significant association was obtained between COVID-19 infection and contact with Covid positive case. Conclusions: Prevalence of COVID-19 infection among Dental and Nursing students was 35.10%. Prevalence of COVID-19 infection among Dental students and Nursing students were 33% and 36% respectively.

Background The benefits of pulmonary rehabilitation (PR) on fatigue-resistant skeletal muscle fibre type I have been found to be smaller in COPD patients with alpha-1 antitrypsin deficiency (AATD) than in those without AATD. Alpha-1 antitrypsin (AAT) augmentation therapy was suggested as a potential factor of influence. Whether this finding mirrors different improvements in 6-min walk distance (6MWD) between both groups remains unknown. Methods 140 patients with AATD-related COPD (phenotype PiZZ, FEV 1 : 31 ± 8%pred.) and 280 COPD patients without AATD (FEV 1 : 31 ± 8%pred.) were matched for baseline 6MWD and included in a retrospective analysis. AATD patients were divided into those “on” (AATD AUG+ ) or “off” (AATD AUG- ) augmentation therapy. 6MWD was assessed pre and post an inpatient 4-week PR program. Plasma level of creatinine was analysed at baseline. Results In AATD and COPD patients with comparable initial 6MWD (331 ± 106 m and 326 ± 101 m, p = n.s.), improvements in 6MWD following PR were similar (+49 ± 49 m and +53 ± 52 m, intra-group change: p AUG+ : +51 ± 55 m, AATD AUG- : +47 ± 40 m, p = n.s.). Only in AATD group, higher baseline creatinine levels and lower 6MWD were positive predictors for the PR-related increase in 6MWD. Conclusions Independently of the genetic variant of AAT, COPD patients achieved the same training-related benefit in 6MWD. Augmentation therapy showed no effect on 6MWD adaptation during PR.

Individuals with Alpha-1 antitrypsin deficiency (AATD) have mutations in the SERPINA1 gene causing genetic susceptibility to early onset lung and liver disease that may result in premature death. Environmental interactions have a significant impact in determining the disease phenotype and outcome in AATD. The aim of this study was to assess the impact of smoke exposure on the clinical phenotype of AATD in Ireland.Clinical demographics and available thoracic computerised tomography (CT) imaging were detected from 139 PiZZ individuals identified from the Irish National AATD Registry. Clinical information was collected by questionnaire. Data was analysed to assess AATD disease severity and evaluate predictors of clinical phenotype.Questionnaires were collected from 107/139 (77%) and thoracic CT evaluation was available in 72/107 (67.2%). 74% of respondents had severe Chronic Obstructive Pulmonary Disease (COPD) (GOLD stage C or D). Cigarette smoking was the greatest predictor of impairment in FEV1 and DLCO (%predicted) and the extent of emphysema correlated most significantly with DLCO. Interestingly the rate of FEV1 decline was similar in ex-smokers when compared to never-smokers. Passive smoke exposure in childhood resulted in a greater total pack-year smoking history. Radiological evidence of bronchiectasis was a common finding and associated with increasing age.The Irish National AATD Registry facilitates clinical and basic science research of this condition in Ireland. This study illustrates the detrimental effect of smoke exposure on the clinical phenotype of AATD in Ireland and the benefit of immediate smoking cessation at any stage of lung disease.

BackgroundDetermining physicians’ awareness about alpha-1 antitrypsin (AAT) deficiency (AATD) may help to explain the discrepancy between the observed and expected number of patients diagnosed with this disease.This study was designed to assess the opinions on knowledge, practice pattern and attitude regarding AATD among physicians in Spain and Portugal.MethodsAn online anonymous survey was performed on pulmonologists (n = 100), internal medicine specialists (IMS) (n = 100) and primary care physicians (PCP) (n = 176). Of the total number of physicians, 221 were from Spain, and 155 were from Portugal. Physicians answered 21 questions related to their personal and professional profile, knowledge regarding AATD and chronic obstructive pulmonary disease (COPD), performance and attitude about AATD, and use of augmentation therapy. Responses were ranked on a 4-point scale indicating the level of agreement. In addition, some of the responses were rated as either “low” or “high” indicating the level of knowledge the respondent felt he/she possessed.ResultsOnly 14 % of physicians reported to “know very well” about AATD (3.3 [SD 0.6] for pulmonologists vs. 2.64 [SD 0.60] for IMS and 2.48 [SD 0.71] for PCP; p < 0.001). Only 45.2 % of physicians correctly answered “<50 mg/dL” as the threshold value of serum AAT to be considered severe AATD (55.0 % of pulmonologists vs. 47.0 % of IMS and 38.6 % of PCP; p = 0.001). Choice of the correct answer did not agree with those physicians self-declaring a high level of AATD knowledge (51.2 %). A total of 43.9 % of physicians correctly identified all diseases or conditions in a list associated or not with AATD. A similar trend was detected when identifying which conditions would be responsive to augmentation therapy (<50 %). Only 15.8 % of specialists performed AATD testing in all patients with COPD (27.0 % pulmonologists, 12.6 % PCP; p = 0.001).ConclusionThe results suggest that a knowledge gap may be contributing to the underdiagnosis of AATD. Physicians in Spain and Portugal showed a marked lack of awareness of their shortcomings in knowledge about AATD, and in general did not follow guidelines and recommendations for AATD testing.