Mild COVID-19 outcomes in adults with inborn errors of immunity: a single-center experience

Currently, 640 million cases of coronavirus disease 2019 (COVID-19) and 6.6 million deaths have been reported world-wide. Risk factors for severe COVID-19 are known, including those with compromised immunity. Among patients with inborn errors of immunity (IEI), early reports of severe outcomes lead to strict masking and social distancing measures. While this resulted in relatively low infection rates among those with IEI, real-world data describing the clinical course of COVID-19 in this patient population have remained limited. We performed a retrospective study of adult IEI patients followed by our center in which a positive test (rapid antigen or PCR) for COVID-19 was determined between November 2021-November 2022. Medical charts were reviewed, and patient interviews conducted. All patients provided informed consent. Twenty-nine patients were enrolled (22 females, 7 males), aged between 18-69 years (median: 20-29 years). The cohort included those with antibody deficiencies (41.37%), combined immunodeficiencies (34.48%;HIES, CARD11, STAT1-GOF), immune dysregulation disorders (20.69%;LRBA deficiency, AIRE deficiency) and phagocyte defect (3.45%;CGD). The duration of symptoms ranged between 3 days-4 weeks (median: < 1 week). Upper respiratory symptoms (including sore throat, congestion) were reported in 97% while fever was present in 41% of patients. Prior to infection, 14 (48%) patients had underlying asthma or bronchiectasis - 2 subsequently experienced shortness of breath and were treated with inhalers or Sotrovimab, respectively. No treatment was required in 65.5% of cases. The remaining received Paxlovid (10.3%), Sotrovimab (13.79%), or antibiotics (10.3%). Of the 2 patients with STAT1-GOF, one tested positive during a repeat episode of febrile neutropenia which required hospitalization. No other patients were hospitalized or needed ICU admission. No deaths were recorded. In light of these favourable outcomes, patients with IEI can gradually and safely return to normal activities.Copyright © 2023 Elsevier Inc.

Autoimmune pulmonary alveolar proteinosis in an adolescent girl with rapidly progressive dyspnea

Autoimmune pulmonary alveolar proteinosis (PAP) is a rare disease, especially in pediatrics, but important to consider, as it may avoid unnecessary and/or invasive investigations and delayed diagnosis. This case report highlights an adolescent girl with rapid onset dyspnea but an unremarkable physical exam and initial testing. However, due to a high index of suspicion, a chest computed tomography (CT) scan was done, revealing a "crazy paving" pattern, which then prompted expedited assessment. This finding, however, is not as specific as often discussed and has a broad differential diagnosis, which will be reviewed in detail as part of this case. Furthermore, this report demonstrates a diagnostic approach for PAP that avoids lung biopsy, previously considered to be required for diagnosis of PAP, but is increasingly becoming unnecessary with more advanced blood tests and understanding of their sensitivity and specificity. Additionally, management strategies for PAP will be briefly discussed.Copyright © 2022 Canadian Thoracic Society.

Posterior Mediastinal Mass: Unraveling a Non-Traumatic Herniation of the Caudate Lobe of the Liver

Introduction: Posterior mediastinal mass is most likely due to neurogenic tumor, meningocele or thoracic spine lesions. Caudate lobe of the liver herniation presenting as posterior mediastinal mass is a rare occurrence. Diaphragmatic herniation (DH) of the caudate lobe presents in various way including dyspnea, dyspepsia or incidental finding on imaging. We present a case of diaphragmatic hernia of the caudate lobe of the liver presenting as a posterior mediastinal mass found during evaluation of dyspnea. Case Description/Methods: A 75-year-old female presented to her physician with worsening shortness of breath from her baseline of 3 days duration. She had a history of sarcoidosis, COVID pneumonia over 1 year ago, COPD, diastolic heart failure, and hypertension. She was initially evaluated for COVID re-infection, which was negative and a CT of the chest with contrast to check for sarcoidosis flare revealed posterior mediastinal mass measuring 4.5 x 6.5 x 6.4 cm. Further work up with CT chest and abdomen with contrast revealed that the posterior mediastinal mass had similar attenuation as the liver and appears continuous with the caudate lobe of the liver. This was confirmed by NM scan of liver. Review of her records from an outside organization revealed similar finding on imaging a few years ago. Patient denied any history of trauma and laboratory work up revealed normal liver functions. After pulmonologist evaluation she was started on 2 L home oxygen following six-minute walk test, and also CPAP following a positive sleep study. Pulmonary function tests were performed and inhalers were continued. Given the chronicity of her symptoms and co-morbidities with stable caudate lobe herniation, conservative management was advised with surgery warranted if symptoms persist despite treatment (Figure 1). Discussion(s): DH is typically found on the left side with stomach or intestine while the right side is usually guarded by the liver. Isolated herniation of part of the liver into the thoracic cavity is rarely reported and is mostly acute from traumatic or spontaneous rupture requiring immediate repair. Our patient was initially evaluated for the posterior mediastinal mass for concerns of tumor, followed by the finding of what was thought to be acute herniation of the caudate lobe of liver into the thoracic cavity. Review of records showed this to be a stable lesion, we suspect that the patient had congenital diaphragmatic defect. Chronic and stable liver herniation into thoracic cavity can be managed conservatively if uncomplicated.

Respiratory support for adult patients with COVID-19

The COVID-19 pandemic is creating unique strains on the healthcare system. While only a small percentage of patients require mechanical ventilation and ICU care, the enormous size of the populations affected means that these critical resources may become limited. A number of non-invasive options exist to avert mechanical ventilation and ICU admission. This is a clinical review of these options and their applicability in adult COVID-19 patients. Summary recommendations include: (1) Avoid nebulized therapies. Consider metered dose inhaler alternatives. (2) Provide supplemental oxygen following usual treatment principles for hypoxic respiratory failure. Maintain awareness of the aerosol-generating potential of all devices, including nasal cannulas, simple face masks, and venturi masks. Use non-rebreather masks when possible. Be attentive to aerosol generation and the use of personal protective equipment. (3) High flow nasal oxygen is preferred for patients with higher oxygen support requirements. Non-invasive positive pressure ventilation may be associated with higher risk of nosocomial transmission. If used, measures special precautions should be used reduce aerosol formation. (4) Early intubation/mechanical ventilation may be prudent for patients deemed likely to progress to critical illness, multi-organ failure, or acute respiratory distress syndrome (ARDS).Copyright © 2020 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of the American College of Emergency Physicians.

A cross-sectional study to evaluate the validity of a novel patient-reported outcome measure of medication adherence in Chronic Obstructive Pulmonary Disease

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterised by a progressive and irreversible decline in lung function. COPD prevalence increased by 44.2% between 1990 and 2015, resulting in 3.2 million deaths globally in 2015.(1) Inhalers are an essential treatment for people living with COPD. However, poor adherence to inhaled medicines is associated with worsening symptom severity, increased hospitalisation, comorbidity, and mortality.(2) Patient Reported Outcome Measures (PROMs) have been designed to examine the factors that contribute to poor medication adherence (MA). To date, none provide a holistic assessment that could be used to design tailored MA interventions. This study sought to address this by evaluating a novel PROM that holistically assesses four key factors of MA referred to as Social, Psychological, Usage, and Rationale, in short, SPUR. Aim(s): To explore the validity of the SPUR model as a holistic PROM of MA in patients living with COPD Methods: This cross-sectional study surveyed adults living with COPD from a large London NHS Trust between January and December 2021. Participants were eligible if they had >=1 inhaler prescribed for a minimum of 6 months prior to the study and were able to read and write in English. Participants who were too clinically unwell to independently complete the survey were excluded, which often included those with a Covid-19 diagnoses. Convenience sampling was used to recruit participants from in-patient wards and the acute admissions unit prior to administration of face-to-face surveys. Survey questions related to socio-clinical data, the SPUR tool, and a previously validated PROM known as the Inhaler Adherence Scale (IAS) that was included as a comparator. The Medication Possession Ratio (MPR), a measure of a patient's pill count in a given time period, was used as an objective comparator of MA. MPR, IAS, and SPUR scores were compared using Spearman's rank correlation coefficient (p). Symptom severity was examined using the COPD Assessment Test (CAT), with a Chi-square analysis (chi2) conducted to explore the relationship between the CAT and SPUR. Result(s): From 123 patients approached for this study, 100 participated providing a response rate of 81.3%. The modal age range was 70-79 years. Participants were predominantly white (90%), educated to GCSE level (51%), and identified as female (52%). Over two thirds (67%) were ex-smokers. SPUR was significantly (p<0.01) and positively correlated with IAS (p=0.65) and MPR (p=0.30), demonstrating that SPUR is a valid measure of MA. Chi-Square analysis identified a significant (p<0.01) relationship between CAT and SPUR scores (chi2=8.570);hence SPUR could reliably identify patients with poorer adherence, which was associated with worsening symptom severity. Conclusion(s): A study strength includes the implementation of an objective measure (MPR) and PROM (IAS) as part of validating SPUR. However, the results should be treated cautiously given the small sample size, which was limited due to Covid-19. This study provides early evidence of SPUR as a reliable holistic measure of MA with significant associations to COPD symptom severity, which could be applied in clinical practice to prospectively address patient outcomes linked to poor MA.

Aerosol Medication Use in COVID-19 Pandemic

Administration of aerolized drugs to patients diagnosed with COVID-19 leads to the risk of transmission of patient-generated infectious aerosols to healthcare providers.While the COVID-19 pandemic is ongoing, in order to provide the best treatment for patients and at the same time to protect healthcare providers at the highest level, it is necessary to increase access to information and pay maximum attention to preventive measures.Copyright © 2020 Bilimsel Tip Yayinevi. All rights reserved.

COPD criteria-led discharge impacts on inpatient COPD management

Introduction/Aim: A chronic obstructive pulmonary disease (COPD) criteria-led discharge (CLD) pathway created on evidence-based guidelines was introduced at Canterbury Hospital to reduce unwanted clinical variation detected during a previous Agency for Clinical Innovation (ACI) audit. This audit aims to review whether adherence to COPD evidence-based guidelines improved after the CLD introduction. Method(s): The electronic medical records of patients admitted to Canterbury Hospital between 14/02/2022 and 01/08/2022 with a diagnosis of COPD, defined as DRG codes E65A and E65B, were reviewed. Data including patient demographics, admission dates, vaccination status, smoking status and cessation counselling, oxygen targets, inhalers, antibiotics, steroids and referrals on discharge were recorded in REDCap. Deidentified data was extracted into excel, grouped based on admission date being pre or post the CLD implementation date of 09/05/2022. The chi square test was used to determine significance. Result(s): A total of 66 patients were included for analysis (n = 25 pre-intervention, n = 39 post-intervention). Appropriate steroid discharge plans and inhaler technique reviews improved post CLD implementation. Antibiotic usage was more consistent with community acquired pneumonia guidelines rather than infective exacerbation of COPD for both groups. Vaccination documentation was generally poor aside from for Coronavirus disease (COVID-19), though there was significant improvement in the discussion of influenza vaccine post CLD. Documentation of oxygen targets did not improve. Referrals to outpatient respiratory services were high in both groups. Conclusion(s): Introduction of a COPD CLD improved adherence to some aspects of COPD evidence-based management at Canterbury Hospital. Further initiatives should be considered targeting appropriate antibiotic usage, oxygen targets and discussion of preventative measures such as vaccination.

Synthesis of the first remdesivir cocrystal: design, characterization, and therapeutic potential for pulmonary delivery.

While cocrystal engineering is an emerging formulation strategy to overcome drug delivery challenges, its therapeutic potential in non-oral applications remains not thoroughly explored. We herein report for the first time the successful synthesis of a cocrystal for remdesivir (RDV), an antiviral drug with broad-spectrum activities against RNA viruses. The RDV cocrystal was prepared with salicylic acid (SA) via combined liquid-assisted grinding (LAG) and thermal annealing. Formation of RDV-SA was found to be a thermally activated process, where annealing at high temperature after grinding was a prerequisite to facilitate the cocrystal growth from an amorphous intermediate, rendering it elusive under ambient preparing conditions. Through powder X-ray analysis with Rietveld refinement, the three-dimensional molecular structure of RDV-SA was resolved. The thermally annealed RDV-SA produced by LAG crystalized in a non-centrosymmetric monoclinic space group P21 with a unit cell volume of 1826.53(17) Å3, accommodating one pair of RDV and SA molecules in the asymmetric unit. The cocrystal formation was also characterized by differential scanning calorimetry, solid-state nuclear magnetic resonance, and Fourier-transform infrared spectroscopy. RDV-SA was further developed as inhaled dry powders by spray drying for potential COVID-19 therapy. The optimized RDV-SA dry powders exhibited a mass median aerodynamic diameter of 4.33 ± 0.2 µm and fine particle fraction of 41.39 ± 4.25 %, indicating the suitability for pulmonary delivery. Compared with the raw RDV, RDV-SA displayed a 15.43-fold higher fraction of release in simulated lung fluid at 120 min (p = 0.0003). RDV-SA was safe in A549 cells without any in vitro cytotoxicity observed in the RDV concentration from 0.05 to 10 µM.

Respiratory Reviews in Asthma 2022.

Asthma is a chronic inflammatory disease of the airways characterized by varying and recurrent symptoms, reversible airway obstruction, and bronchospasm. In this paper, clinical important studies on asthma published between March 2021 and February 2022 were reviewed. A study on the relationship between asthma and chronic rhinosinusitis, bronchiectasis, and hormone replacement therapy was published. A journal on the usefulness of fractional exhaled nitric oxide for the prediction of severe acute exacerbation was also introduced. Studies on the effect of inhaler, one of the most important treatments for asthma, were published. Studies on the control of severe asthma continued. Phase 2 and 3 studies of new biologics were also published. As the coronavirus disease 2019 (COVID-19) pandemic has been prolonged, many studies have explored the prevalence and mortality of COVID-19 infection in asthma patients.

Clinical Approaches to Minimize Readmissions of Patients with COPD: A Narrative Review

Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease and also a lead-ing cause of morbidity and mortality worldwide. The frequent readmissions of patients with COPD may reduce lung function, mental health, and quality of life;it also increases the cost of treatment and mortality rate. Some common factors that may increase the readmission frequency of COPD patients include delay of diagnosis, advanced lung function decline, lack of adherence for COPD treatment, ineffective management of comorbidities, acute exacerbation or stable COPD, and infec-tions. However, these factors might be well controlled with appropriate approaches to minimize the readmission of patients with COPD. In this review, we propose a strategy with a seven-step approach to reduce the readmission in COPD patients, including early diagnosis of COPD, optimal treatment for stable COPD, targeted management of comorbidities, adequate therapy for acute ex-acerbations, individualized action plans for COPD patients, effective prevention of bacterial and viral infections, and adaptive program of pulmonary rehabilitation. Thus, implementing this approach may reduce the risk of readmission in patients with COPD.Copyright © 2023 Bentham Science Publishers.

Leser-Trelat sign: can it follow COVID-19 infection?

Seborrhoeic keratosis is a benign brownish-black skin lesion that is almost always seen in middle-aged and elderly populations. The sudden onset and rapid increase in size and/ or number of seborrhoeic keratoses is called the Leser-Trelat sign, suggesting a paraneoplastic manifestation of internal malignancy. However, eruptive seborrhoeic keratoses are also described in some nonmalignant conditions such as human papillomavirus infection and HIV infection. Herein, we report a case with Leser-Trelat sign in a patient following COVID-19 infection. A 50-year-old man presented to our dermatology clinic complaining of the sudden appearance of multiple warty-like lesions on his back, which had occurred 2 months after recovery from COVID-19 infection. According to his medical history, the patient presented with cough, fever and dyspnoea about 2 months prior to the appearance of his skin lesions. He was referred to a health centre, where a nasopharyngeal swab was taken, and his polymerase chain reaction test for COVID-19 was positive. In addition, bilateral patchy ground-glass infiltration was reported in his high-resolution computed tomography (HRCT) scan, all in favour of COVID- 19 infection. The patient was then treated with acetaminophen, dexamethasone (intramuscular injection), salmeterol and a fluticasone inhaler, and his symptoms improved. Two months after recovery from his mild COVID-19 infection, several small asymptomatic pigmented verrucous papules appeared on his back. Physical examination revealed multiple rough, oval-shaped, brownish papules of varying size. Dermatoscopy of the lesions was also performed. Both clinical and dermoscopic findings were in favour of seborrhoeic keratosis. In order to reach a final diagnosis, a skin biopsy was performed, and microscopic examination of the biopsy specimen showed hyperkeratosis and well-defined epidermal hyperplasia composed mainly of the proliferation of benignlooking basaloid cells and fewer squamoid cells and horn cysts and increased melanin, mostly at the dermoepidermal junction. The dermis showed no significant change. Based on the above findings, the patient was diagnosed with eruptive seborrhoeic keratosis. To determine the possible cause of this eruption, the patient was further evaluated. In his past medical history, he was generally healthy before his COVID-19 infection and had no history of comorbidities. The patient underwent a workup to rule out any internal malignancies. Laboratory tests revealed normal results and included a complete blood count, liver and kidney function tests, electrolytes, prostate-specific antigen and urine analysis. Gastrointestinal endoscopy and colonoscopy ruled out any gastrointestinal malignancy. Chest X-ray and HRCT revealed no malignant lesion. In addition, the patient's abdominopelvic sonography was normal. The patient had no family history of similar skin lesions and gave no history of any chronic inflammatory skin diseases or viral conditions. Therefore, the appearance of the Leser-Trelat sign after COVID- 19 infection was a possibility in this patient. The role of transforming growth factor-alpha and tumour necrosis-alpha in eruptive seborrhoeic keratoses, as well as in COVID-19 infection, can be a common area of interest to explore in the aetiology of this entity.

EVALUATION OF THE ASSOCIATION BETWEEN PROPER INHALER TECHNIQUE AND ANXIETY IN CHEST DISEASES OUTPATIENT CLINIC PATIENTS DURING COVID-19 PANDEMIC: A PROSPECTIVE CROSS-SECTIONAL STUDY

Objective: In this study, we aimed to investigate the association between inhaler use skills and general anxiety or coronavirus anxiety scores in patients with respiratory diseases. Material and Method: Inhaler techniques of 70 asthma and chronic obstructive pulmonary disease (COPD) patients were evaluated by three clinical pharmacists. A pulmonologist assessed the patients' anxiety scores using the Hamilton Anxiety Rating Scale (HAM-A) and Coronavirus Anxiety Scale (CAS). We used IBM SPSS 25.0 as a software program for related statistical analysis Result and Discussion: Proper inhaler technique wasn't found to be associated with CAS score, age, comorbidity, inhaler type. HAM-A stage (p=0.096) and educational status (p=0.074) were not found as statistically significant in affecting the proper inhaler technique. A weak correlation was found between age and CAS score (r=-0.278, p=0.02). Asthma patients have a higher rate of coronavirus anxiety than COPD patients (p=0.036). Female patients had higher HAM-A (p=0,037) and CAS scores (p=0,002) than male patients. There was a moderate correlation between HAM-A and CAS scores (r=0.407, p<0.001). The correlation between HAM-A and inhaler use skills scores were not found in statistical significance (r=-0.208, p=0.083). In conclusion, increase of CAS score wasn't found to be associated with proper inhaler technique. HAM-A score was found to affect proper inhaler technique negatively, but these results are not significant. © 2022 Authors. All rights reserved.

Exploring use of a connected Internet-Of-Things system (A4A+) with CE-marked devices to support asthma selfmanagement? A mixed method study

Background: In the COVID pandemic, patients have had to rely on remote consultations to help them to live with their condition. Aim(s): We aimed to explore how a connected system (A4A+) linking smart devices (inhaler/watch/peak flow meter) could support asthma self-management. Method(s): The A4A+ system collected data from smart devices that could be shared with practices in a pdf attached to patients' electronic health records. We recruited 10 patients via social media, observed their usage of the system over a month, and undertook baseline and exit interviews. We also interviewed 3 GPs and an asthma nurse for their views on the report format. Thematic analysis used the Unified Theory of Acceptance and Use of Technology (UTAUT) model. Result(s): 7517 self-management data-points (asthma symptoms, PEFR, inhaler usage, exercise intensity, heart rate, sleeping pattern, body/air temperature) were collected from 10 patients though recording reduced over the month. Most patients chose to monitor their reliever inhaler rather than the preventer. Patients felt 'positive', found it 'easy' to use the system and chose to use devices they thought were "accurate". Monitoring adjustments to medication, having asthma (or COVID) symptoms triggered and motivated them to adopt the system. Clinicians wanted an overall asthma score/status and reliever usage on the report. Conclusion(s): A connected system could enable flexible digital approaches to care by providing on-going selfmanagement data to support remote consultation. However, providing users with confidence in the 'accuracy' of systems is needed to maintain patients' motivation to use the system.

An Enhanced Dissolving Cyclosporin-A Inhalable Powder Efficiently Reduces SARS-CoV-2 Infection In Vitro.

This work illustrates the development of a dry inhalation powder of cyclosporine-A for the prevention of rejection after lung transplantation and for the treatment of COVID-19. The influence of excipients on the spray-dried powder's critical quality attributes was explored. The best-performing powder in terms of dissolution time and respirability was obtained starting from a concentration of ethanol of 45% (v/v) in the feedstock solution and 20% (w/w) of mannitol. This powder showed a faster dissolution profile (Weibull dissolution time of 59.5 min) than the poorly soluble raw material (169.0 min). The powder exhibited a fine particle fraction of 66.5% and an MMAD of 2.97 µm. The inhalable powder, when tested on A549 and THP-1, did not show cytotoxic effects up to a concentration of 10 µg/mL. Furthermore, the CsA inhalation powder showed efficiency in reducing IL-6 when tested on A549/THP-1 co-culture. A reduction in the replication of SARS-CoV-2 on Vero E6 cells was observed when the CsA powder was tested adopting the post-infection or simultaneous treatment. This formulation could represent a therapeutic strategy for the prevention of lung rejection, but is also a viable approach for the inhibition of SARS-CoV-2 replication and the COVID-19 pulmonary inflammatory process.

The lived experience of adherence to asthma medication in young adults (18-34 years).

BACKGROUND: Adherence to asthma medications is commonly poor and is the primary cause for anticipated worsening health outcomes for patients with asthma. Worldwide, qualitative investigations that examine the adherence of young adults (18-34 years) to their asthma medication are limited. METHOD: This study used a phenomenological research approach to explicate the experience of asthma medication adherence as described by young adults. Data were collected using semi-structured in-depth video interviews conducted with participants aged between 18 and 34 years to elicit their lived experience with adherence to asthma medication. Data from the interviews were transcribed and analyzed using the Edward and Welch (1) extension of Colaizzi's approach to phenomenology. RESULTS: Results yielded four main themes related to the phenomenon of adherence that emerged from the analysis. The themes were: Having a plan; Having knowledge about your medication and asthma triggers; Being responsible with asthma medication; and Health belief. CONCLUSION: According to the findings, for young people adhering to asthma medication is a process that depends on four vital aspects: (A) plan, (B) knowledge, (C) responsibility, and (D) belief. If young adults with asthma received individualized written asthma plans and have adequate knowledge about this plan, developing the correct health belief is likely to result. Hence, this can lead to a greater responsibility to manage their asthma to the recommended adherence level.

Asthma Management Among Children With Food Allergy in the FORWARD Study During COVID-19

Rationale: Asthma remains a significant comorbidity among children with food allergy (FA). Longitudinal data on the course of asthma in this population, particularly during the COVID-19 pandemic, is lacking. This study aims to describe asthma management and control among children with FA during the COVID-19 pandemic. Methods: Children with FA (≤12 years old at enrollment) were enrolled into FORWARD, a prospective, observational cohort study. Data from participants with FA and asthma who completed a 12-month and 24-month post-enrollment asthma therapy assessment were included (n=125). Surveys were administered between January 2019 - July 2022, which includes the onset and duration of COVID-19. Responses to the same questions at the two time points were analyzed using tests of exact symmetry. Results: Compared to the 12-month survey, caregivers at the 24-month survey more frequently reported that their children were not using their inhaler for quick relief (1.6% vs. 9.4%, p = 0.008) and were using their medication incorrectly (3.2% vs. 8.7%, p = 0.003). They less frequently reported that they were unsure whether their medications were useful (3.2% vs. 0.0%, p = 0.016). A similar distribution was observed when non-Hispanic Black and non-Hispanic White participants were compared. No significant differences were evident when comparing symptoms. Conclusions: The symptom burden of asthma remained stable even during the pandemic. However, during this time, children with asthma were less likely to need a rescue inhaler and to be adherent to their maintenance regimen. Further longitudinal research on asthma management is necessary to better understand the potential impact of COVID-19.