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Introducción: El asma es una entidad con alta prevalencia a nivel mundial y en Cuba, que ha suscitado nuevas investigaciones. Objetivo: Caracterizar la producción científica cubana sobre asma en la base de datos Scopus. Materiales y métodos: Se realizó un estudio observacional, descriptivo y bibliométrico de los artículos publicados sobre asma en Scopus con autores cubanos, desde 1973 hasta 2021. Para la recuperación de los registros se empleó una fórmula de búsqueda. Para el análisis de los datos se usaron los software Bibexcel y VOSviewer. Resultados: Se publicaron 154 investigaciones sobre asma, con predominio de artículos originales (136) y de revisión (12). Las áreas más productivas fueron Medicina (144) e Inmunología y Microbiología (34). Los artículos fueron publicados en 48 revistas; de ellas, 11 fueron cubanas, con la Revista Cubana de Medicina como la más productiva. México aportó el mayor número de colaboraciones (10). El Hospital Clínico Quirúrgico Docente General Calixto García (15) fue el más productivo. Se identificaron tres clústeres de palabras clave, con "human", "asthma" y "Cuban" como términos centrales y de mayor ocurrencia. Conclusiones: Existió una baja producción científica sobre asma, centrada principalmente en artículos originales, en el área de Medicina y en revistas nacionales. Se evidenció colaboración internacional. Los ejes principales de investigación fueron el diagnóstico, tratamiento, investigación básica en modelos animales, nuevas terapéuticas, factores de riesgo y prevención.

Introduction: Asthma is an entity with high prevalence worldwide and in Cuba, which has prompted new research. Objective: To characterize Cuban scientific production on asthma in the Scopus database. Materials and methods: An observational, descriptive and bibliometric study was carried out on articles on asthma published in Scopus by Cuban authors, from 1973 to 2021. A search formula was used to retrieve the records. Bibexcel and VOSviewer were used for data analysis. Results: 154 research papers on asthma were published; with a predominance of original (136) and review articles (12). The most productive areas were Medicine (144) and Immunology and Microbiology (34). Articles were published in 48 journals, of which 11 were Cuban, with the Revista Cubana de Medicina (Cuban Journal of Medicine) being the most productive. Mexico contributed the highest number of collaborations (10). The Teaching Hospital General Calixto García (15) was the most productive. 3 key word clusters were identified, with "human", "asthma" and "Cuban" as central and most occurring terms. Conclusions: There was a low scientific production on asthma, mainly focused on original articles, in the area of Medicine and in national journals. International collaboration was evident. The main areas of research were diagnosis, treatment, basic research in animal models, new therapeutics, risk factors and prevention.

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BACKGROUND: Various trajectories for lung function and bronchial hyper-reactivity (BHR) from early childhood to adulthood are described, including puberty as a period with excessive lung growth. Bronchiolitis in infancy may be associated with increased risk of developing chronic obstructive pulmonary disease, but the development of respiratory patterns during puberty is poorly characterized for these children. We aimed to study the development and trajectories of lung function and BHR from 11 to 18 years of age in children hospitalized for bronchiolitis in infancy. METHODS: Infants hospitalized for bronchiolitis at the University Hospitals in Stavanger and Bergen, Norway, during 1997-1998, and an age-matched control group, were included in a longitudinal follow-up study and examined at 11 and 18 years of age with spirometry and methacholine provocation test (MPT). The MPT data were managed as dose-response slope (DRS) in the statistical analyses. Changes in lung function and DRS from 11 to 18 years of age were analyzed by generalized estimating equations, including interaction terms. RESULTS: z-scores for forced vital capacity (FVC), forced expiratory volume in first second (FEV1 ), FEV1 /FVC ratio, and DRS were not different from 11 to 18 years of age in both the post-bronchiolitis and the control group. The trajectories from 11 to 18 years did not differ between the two groups. BHR at age 11 was independently associated with asthma at age 18. CONCLUSION: Children hospitalized for bronchiolitis had stable predicted lung function and BHR from 11 to 18 years of age. The lung function trajectories were not different from controls.

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BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) and asthma are associated, and nocturnal breathing difficulty that is usually identified as asthma-like symptoms can be present in both conditions. We investigated how nocturnal asthma-like symptoms (NAS) and bronchial hyper-reactivity (BHR) contribute to the association between OSA risk and current asthma, which is currently unknown but a clinically important question. METHODS: We used data from 794 middle-aged participants in a population-based cohort who provided information on OSA risk (defined by a STOP-Bang questionnaire score of at least 3), current asthma and NAS, and underwent methacholine bronchial challenge testing. Using regression models, we examined the association between OSA risk and current asthma-NAS subgroups and investigated any effect modification by BHR. RESULTS: The participants were aged 50 years (49.8% male). OSA risk was associated with NAS with or without current asthma (odds ratio (OR): 2.6; 95% CI = 1.3-5.0; OR: 4.2; 95% CI = 1.1-16.1, respectively), but not with current asthma in the absence of NAS. BHR was associated with current asthma with or without NAS (OR: 2.9; 95% CI = 1.4-5.9; OR: 3.4; 95% CI = 2.0-7.0, respectively) but not with NAS in the absence of current asthma. The associations between OSA risk and current asthma were neither modified nor mediated by BHR. CONCLUSION: Our findings suggest that some of the nocturnal symptoms perceived as asthma may be OSA symptoms. Patients with nocturnal asthma symptoms should be considered for possible OSA.

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BACKGROUND: Hopkins syndrome (HS) is a rare disorder presenting with acute flaccid paralysis of the limbs following an asthma attack. Neurologists encounter a diagnostic challenge if patients without a history of bronchial asthma develop neurologic features mimicking HS following acute respiratory distress. We report a case of HS occurring after a first episode of bronchial asthma associated with enterovirus D68 infection. CASE PRESENTATION: A 5-year-old girl developed acute respiratory distress. On the fourth hospital day, both her legs became paralyzed except for slight muscle contraction in the right lower limb. Tendon reflexes in the lower limbs were diminished and there was a positive Babinski sign on the right. Sensation was normal in all modalities, and there was no uro-rectal disturbance. Spinal magnetic resonance imaging identified T2-hyperintense lesions with spinal cord edema, mainly involving the bilateral T11 to L1 anterior horns, with left side dominance extending to the left posterior horn. The neurological and neuro-radiological findings of our case were suggestive of HS; however, she had no history of bronchial asthma. An acetylcholine inhalation challenge eventually proved the presence of reversible airway hyper-responsiveness, allowing us to diagnose HS. We identified enterovirus D68 in the patient's intratracheal aspirates using a sensitive polymerase chain reaction assay. Intravenous immunoglobulin administrations at 2 g/kg2 for 5 consecutive days were repeated every month up to four times. After these treatments, the muscle strength of her right lower limb slightly improved while her left lower leg remained completely paralyzed. CONCLUSION: This case emphasizes the importance of provocation tests to reveal the presence of airway hyper-responsiveness when a child shows neurological signs mimicking HS following acute respiratory distress. Furthermore, the present case suggests a possible link between HS and acute flaccid paralysis following lower respiratory tract infection by enterovirus D68.

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OBJECTIVE: Little is known of the subjective response to exercise that involves short "all out" bursts of effort, separated by recovery periods (sprint interval exercise (SPRINT)) among adults with exercise-induced bronchoconstriction (EIBC). The purpose of this study was to compare subjective responses to SPRINT and moderate intensity continuous exercise (MOD) among adults with EIBC, and to compare these responses between adults with EIBC and those without EIBC. METHODS: Eight adults (22.3 ± 3.0 years) with EIBC, and eight adults (22.3 ± 3.0 years) without EIBC completed a SPRINT (4 × 30 second sprints separated by 4.5 minutes of active recovery) and MOD (20 minutes at 65% peak power output) session in random order. Self-reported affect, perceived breathlessness, and perceived exertion were recorded throughout exercise using validated scales. Enjoyment was assessed following exercise. RESULTS: Differences between SPRINT and MOD were observed such that affect and perceived breathlessness were worse during the initial stages of SPRINT than MOD; however, differences disappeared by the end of exercise. Enjoyment was similar for SPRINT and MOD in the EIBC group (SPRINT: 72.9 ± 20.0 vs. MOD: 79.5 ± 20.5, p = 0.25), and between groups for SPRINT and MOD. CONCLUSIONS: Perceived breathlessness may impact affect during the early stages of exercise among those with EIBC. Post-exercise enjoyment appears to be similar between SPRINT and MOD. Future research is needed to better understand the relationship between ventilation patterns, exercise intensity, and enjoyment of exercise among those with EIBC.

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BACKGROUND: Children with asthma may be less physically active than their healthy peers. We aimed to investigate whether perceived exercise limitation (EL) was associated with lung function or bronchial hyper-responsiveness (BHR), socioeconomic factors, prenatal smoking, overweight, allergic disease, asthma severity, or physical activity (PA). METHODS: The 302 children with asthma from the 10-year examination of the Environment and Childhood Asthma birth cohort study underwent a clinical examination including perceived EL (structured interview of child and parent(s)), measure of overweight (body mass index by sex and age passing through 25 kg/m2 or above at 18 years), exercise-induced bronchoconstriction (forced expiratory volume in one-second (FEV1 ) pre- and post-exercise), methacholine bronchial challenge (severe BHR; provocative dose causing ≥20% decrease in FEV1 ≤ 1 µmol), and asthma severity score (dose of controller medication and exacerbations last 12 months). Multivariate logistic regression analyses were conducted to assess associations with perceived EL. RESULTS: In the final model explaining 30.1%, asthma severity score (OR: 1.49, (1.32, 1.67)) and overweight (OR: 2.35 (1.14, 4.82)) only were significantly associated with perceived EL. Excluding asthma severity and allergic disease, severe BHR (OR: 2.82 (1.38, 5.76)) or maximal reduction in FEV1 post-exercise (OR: 1.48 (1.10, 1.98)) and overweight (OR: 2.15 (1.13, 4.08) and 2.53 (1.27, 5.03)) explained 9.7% and 8.4% of perceived EL, respectively. CONCLUSIONS: Perceived EL in children with asthma was independently associated with asthma severity and overweight, the latter doubling the probability of perceived EL irrespectively of asthma severity, allergy status, socioeconomic factors, prenatal smoking, or PA.

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INTRODUCTION: Small airway dysfunction occurs following WTC dust exposure, but its role in producing symptoms is unclear. METHODS: Methacholine challenge (MCT) was used to assess the relationship between onset of respiratory symptoms and small airway abnormalities in 166 symptomatic WTC dust-exposed patients. Forced oscillation testing (FOT) and respiratory symptoms were assessed during MCT. FOT parameters included resistance at 5 and 20 Hz (R5 and R20 ) and the R5 minus R20 (R5-20 ). RESULTS: Baseline spirometry was normal in all (mean FEV1 100 + 13% predicted, mean FEV1 /FVC 80 + 4%). MCT revealed bronchial hyperreactivity by spirometry in 67 patients. An additional 24 patients became symptomatic despite minimal FEV1 change (<5%); symptom onset coincided with increased R5 and R5-20 (P > 0.001 vs. baseline). The dose-response of FOT (reactivity) was greater compared with subjects that remained asymptomatic (P < 0.05). CONCLUSIONS: FOT during MCT uncovered reactivity in small airways as a mechanism for respiratory symptoms in subjects with inhalational lung injury. Am. J. Ind. Med. 59:767-776, 2016. © 2016 Wiley Periodicals, Inc.

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It has been known for many years that multiple early life factors can adversely affect lung function and future respiratory health. This is the first systematic review to attempt to analyse all these factors simultaneously. We adhered to strict a priori criteria for inclusion and exclusion of studies. The initial search yielded 29,351 citations of which 208 articles were reviewed in full and 25 were included in the review. This included 6 birth cohorts and 19 longitudinal population studies. The 25 studies reported the effect of 74 childhood factors (on their own or in combinations with other factors) on subsequent lung function reported as percent predicted forced expiration in one second (FEV1). The childhood factors that were associated with a significant reduction in future FEV1 could be grouped as: early infection, bronchial hyper-reactivity (BHR) / airway lability, a diagnosis of asthma, wheeze, family history of atopy or asthma, respiratory symptoms and prematurity / low birth weight. A complete mathematical model will only be possible if the raw data from all previous studies is made available. This highlights the need for increased cooperation between researchers and the need for international consensus about the outcome measures for future longitudinal studies.

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BACKGROUND: Viral bronchiolitis in infancy has been associated with increased bronchial reactivity and reduced lung function in later childhood and even in adulthood. However, lung function at preschool age is less studied, mainly due to technical difficulties. The purpose of the study was to evaluate lung function and bronchial reactivity at preschool age in children who were hospitalized for bronchiolitis in early infancy. SUBJECTS AND METHODS: Airway resistance and reactance, and bronchial reactivity to exercise were studied with impulse oscillometry (IOS) at the mean age of 6.3 years in 103 children hospitalized for bronchiolitis at less than 6 months of age. RESULTS: In baseline lung-function measurement, resistance (n = 8; 7.8%) or reactance (19; 18.4%) at 5 Hz were pathological in 20% of children compared to Finnish population-based height-adjusted reference values. Increased bronchial reactivity by exercise challenge (5; 4.9%) or bronchodilatation (11; 10.7%) tests was present in 16%. Irreversible changes were revealed in only one case. CONCLUSIONS: Though reduced lung function and increased airway reactivity were rather common, evidence for persistent lung function reduction was rare, less than 1%, at preschool age in children hospitalized for bronchiolitis caused mainly by respiratory syncytial virus at age less than 6 months.

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BACKGROUND: The small airways are an important site of inflammation in asthma. However, the relation between small airway dysfunction and clinical expression of asthma has hardly been studied. AIM: To investigate the association of small and large airway dysfunction with asthma symptoms and bronchial hyper-responsiveness (BHR). METHODS: Fifty-eight patients with asthma were characterized with spirometry, body plethysmography, impulse oscillometry, alveolar and bronchial exhaled nitric oxide, and a methacholine provocation. Symptoms of nocturnal asthma, exercise-related symptoms, BHR symptoms, and respiratory symptoms were assessed with the Asthma Control Questionnaire and Bronchial Hyper-responsiveness Questionnaire. Perception of dyspnea was rated with the Borg score during the provocation test. RESULTS: Small and large airway dysfunction did not associate with higher scores for nocturnal, exercise-related, or BHR symptoms. Only higher scores on wheezing were significantly associated with higher values of difference between R5 and R20 (R5-R20) (r = 0.367, P < 0.01) and AX (r = 0.354, P < 0.01). Lower FEF25-75% (P = 0.024) and higher R5-R20 (P = 0.003) values were independently associated with more severe BHR to methacholine, but not FEV1 or R20 values. The increase in dyspnea during the methacholine provocation was strongly and independently correlated with the decrease in FEV1 and reactance of the respiratory system at 5 Hertz. CONCLUSION: Small and large airway dysfunction poorly associate with asthma symptoms in our patients. However, deteriorations in small airway dysfunction are strongly related to an increase in dyspnea during bronchial provocation with methacholine. Small airway dysfunction contributes also independently to the clinical expression of asthma, as reflected by the severity of BHR.

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BACKGROUND: Fingolimod (FTY) mediates bronchoconstriction by interacting with sphingosine-1-phosphate receptors. The majority of the reported adverse respiratory events occur during the first weeks of treatment. CASE PRESENTATION: A 49-year-old woman developed a life-threatening asthma attack after 6 months of continuous FTY treatment. The adverse event required prolonged hospitalization, and the patient recovered without sequelae after FTY interruption. A history of previous airway hyperreactivity and a concurrent viral respiratory infection possibly acted as predisposing factors. CONCLUSION: This first description of a severe, life-threatening asthma attack during prolonged FTY treatment suggests the need for long-term clinical surveillance, especially in patients with known predisposing factors.

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AIM: To assess whether inflammatory markers measured in urine and blood during acute bronchiolitis in infancy were associated with asthma, lung function, bronchial hyper-responsiveness (BHR) and atopy at 11 years of age. METHODS: We included 105 children hospitalised for bronchiolitis during their first year of life. At hospitalisation, urinary (U-) eosinophil protein X, U-leukotriene E4 , U-prostaglandin 9α, 11ß-PGF2 and blood eosinophil counts were measured. Ninety-five children (90%) were available for follow-up at 11 years of age. RESULTS: At follow-up, higher blood eosinophil counts obtained during bronchiolitis were observed in the group with asthma than in the group without asthma (median 0.27 versus 0.09 × 10(9) /L, respectively, p = 0.048). By regression analyses, blood eosinophil counts during the acute bronchiolitis were positively associated with BHR (p = 0.006) and negatively associated with forced expiratory volume in first second (p = 0.025) at 11 years of age. None of the other inflammatory markers were associated with asthma, lung function, BHR or atopy at 11 years of age. CONCLUSION: Eosinophil inflammation during bronchiolitis may have a long-term impact on lung function and airway responsiveness. The associations could be related to virus-host interactions during bronchiolitis or to predisposed children.

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BACKGROUND AND OBJECTIVES: Bronchodilator reversibility and diurnal peak flow variability are considered characteristic of asthma patients. Patients with chronic obstructive pulmonary disease (COPD) show poor reversibility. But reversibility and variability in other pulmonary diseases manifesting with airflow obstruction in not known. Therefore, we assessed reversibility and peak flow variability in patients with various lung diseases to recognize the pattern. MATERIALS AND METHODS: Seventy consecutive patients with a diagnosis of lung diseases manifesting with airflow obstruction were recruited in the study. These included 23 patients with asthma, 11 patients with bronchiectasis, 16 patients with post-tubercular lung disease (PTLD), and 20 patients with COPD. Ten healthy matched control subjects were also selected to pair with asthmatic patients. Bronchodilator reversibility test was done initially and peak expiratory flow rate (PEFR) was measured for a duration of 1 week by patients themselves on a chart that was given to them. The mean amplitude percentage of these records were analyzed. RESULTS: The mean values of peak flow variability were 14.73% ± 6.1% in asthmatic patients, 11.98% ± 7.5% in patients with bronchiectasis, and 10.54% ± 5.3% in PTLD. The difference in the mean values of peak flow variability between asthma and bronchiectasis, that is, 14.73 (6.1) vs 11.98 (7.5) was not statistically significant (P > 0.05). Forced expiratory volume one second (FEV(1)) reversibility values were 14.77% ± 26.93%, 11.24% ± 20.43%, 10.85% ± 13.02%, 16.83% ± 22.84%, and 5.47% ± 4.99% in asthma, COPD, PTLD, bronchiectasis, and healthy subjects, respectively. CONCLUSION: Both reversibility and diurnal peak flow variability were higher in patients with various lung diseases compared with normal healthy subjects. Although these are characteristic of asthma, some cases of bronchiectasis and PTLD patients may also manifest asthma-like PEFR variability and reversibility.

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BACKGROUND: Ulcerative colitis is an inflammatory chronic disease which is believed to be a multi organ condition. The prevalence of ulcerative colitis is reportedly increasing in Iran presenting with the same clinical characteristics as in developing countries. Pulmonary manifestations of ulcerative colitis are increasingly reported. In this study, we investigated the incidence of bronchial hyper-responsiveness (BHR) in ulcerative colitis (UC) patients. MATERIALS AND METHODS: Fifty-one UC patients with definite diagnosis referred to Shariati Hospital, Tehran, Iran, were selected to be evaluated with methacholine challenge test from October 2010 to October 2011. Patients were compared for their methacholine test outcome and its association with age, sex, diagnosis time, and disease activity. RESULTS: The median age was 41 (range 15 to 65) years. The median time of diagnosis was 7 (range <1 to 16) years. Forty-five percent were females, 18% had active disease and 13% had comorbidity. Nine percent of patients with UC had abnormal PFT in our study. Three cases (5%) had bronchial hyper-responsiveness that was not correlated with sex, age, time of diagnosis, or disease activity. CONCLUSION: A small number of ulcerative colitis patients in our study had disturbed pulmonary function test which is in concord with the findings of other studies. However, higher rates of bronchial hyper-responsiveness have been reported in other studies. Confounding factors like cigarette smoking and medications, which were negative or minimal in our study, may influence the results.

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Hydroxyapatite is commonly used as a filler to replace amputated bone or as a coating to promote bone ingrowth into prosthetic implants. Many modern implants, such as hip replacements and dental implants, are coated with hydroxyapatite. We report a patient with occupational asthma due to hydroxyapatite, proven by a specific inhalation challenge, who experienced an early asthmatic reaction after exposure to hydroxyapatite, without increased airway responsiveness to methacholine despite an increased eosinophil count in the peripheral blood. A 38-year-old male dental implant worker visited our allergy department for the evaluation of occupational asthma. He had treated dental implant titanium surfaces with hydroxyapatite for 1.5 years. One year after starting his employment, he noticed symptoms of rhinorrhea, paroxysmal cough, and chest tightness. His symptoms were aggravated during and shortly after work and subsided several hours after work. When he stopped working for 2 months because of his chest symptoms, he became asymptomatic. After restarting his work, his symptoms reappeared and were aggravated. A methacholine bronchial challenge test had a negative response. The following day, a specific bronchial provocation test with wheat powder was negative. On the third day, a specific bronchial provocation test with hydroxyapatite powder produced an early asthmatic response. On the fourth day, a methacholine bronchial challenge test was negative. Further studies are needed to evaluate the exact pathogenetic mechanism of hydroxyapatite-induced occupational asthma.

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Hydroxyapatite is commonly used as a filler to replace amputated bone or as a coating to promote bone ingrowth into prosthetic implants. Many modern implants, such as hip replacements and dental implants, are coated with hydroxyapatite. We report a patient with occupational asthma due to hydroxyapatite, proven by a specific inhalation challenge, who experienced an early asthmatic reaction after exposure to hydroxyapatite, without increased airway responsiveness to methacholine despite an increased eosinophil count in the peripheral blood. A 38-year-old male dental implant worker visited our allergy department for the evaluation of occupational asthma. He had treated dental implant titanium surfaces with hydroxyapatite for 1.5 years. One year after starting his employment, he noticed symptoms of rhinorrhea, paroxysmal cough, and chest tightness. His symptoms were aggravated during and shortly after work and subsided several hours after work. When he stopped working for 2 months because of his chest symptoms, he became asymptomatic. After restarting his work, his symptoms reappeared and were aggravated. A methacholine bronchial challenge test had a negative response. The following day, a specific bronchial provocation test with wheat powder was negative. On the third day, a specific bronchial provocation test with hydroxyapatite powder produced an early asthmatic response. On the fourth day, a methacholine bronchial challenge test was negative. Further studies are needed to evaluate the exact pathogenetic mechanism of hydroxyapatite-induced occupational asthma.

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