Restrictive Lung Impairment Research Articles

Long-term respiratory follow-up of ICU hospitalized COVID-19 patients: Prospective cohort study.

Coronavirus disease (COVID-19) survivors exhibit multisystemic alterations after hospitalization. Little is known about long-term imaging and pulmonary function of hospitalized patients intensive care unit (ICU) who survive COVID-19. We aimed to investigate long-term consequences of COVID-19 on the respiratory system of patients discharged from hospital ICU and identify risk factors associated with chest computed tomography (CT) lesion severity. A prospective cohort study of COVID-19 patients admitted to a tertiary hospital ICU in Brazil (March-August/2020), and followed-up six-twelve months after hospital admission. Initial assessment included: modified Medical Research Council dyspnea scale, SpO2 evaluation, forced vital capacity, and chest X-Ray. Patients with alterations in at least one of these examinations were eligible for CT and pulmonary function tests (PFTs) approximately 16 months after hospital admission. Primary outcome: CT lesion severity (fibrotic-like or non-fibrotic-like). Baseline clinical variables were used to build a machine learning model (ML) to predict the severity of CT lesion. In total, 326 patients (72%) were eligible for CT and PFTs. COVID-19 CT lesions were identified in 81.8% of patients, and half of them showed mild restrictive lung impairment and impaired lung diffusion capacity. Patients with COVID-19 CT findings were stratified into two categories of lesion severity: non-fibrotic-like (50.8%-ground-glass opacities/reticulations) and fibrotic-like (49.2%-traction bronchiectasis/architectural distortion). No association between CT feature severity and altered lung diffusion or functional restrictive/obstructive patterns was found. The ML detected that male sex, ICU and invasive mechanic ventilation (IMV) period, tracheostomy and vasoactive drug need during hospitalization were predictors of CT lesion severity(sensitivity,0.78±0.02;specificity,0.79±0.01;F1-score,0.78±0.02;positive predictive rate,0.78±0.02; accuracy,0.78±0.02; and area under the curve,0.83±0.01). ICU hospitalization due to COVID-19 led to respiratory system alterations six-twelve months after hospital admission. Male sex and critical disease acute phase, characterized by a longer ICU and IMV period, and need for tracheostomy and vasoactive drugs, were risk factors for severe CT lesions six-twelve months after hospital admission.

Evaluation of Ventilatory Functions in Hypothyroid Patients

Introduction Respiratory muscle weakness is proportional to the degree of thyroid function and is reversible by replacement therapy with thyroxine. Aim To evaluate the changes in pulmonary functions in newly diagnosed hypothyroid patients as compare with healthy controls by spirometry and to observe the improvement in pulmonary functions after hormone replacement therapy. Patients and methods A total of 30 newly diagnosed hypothyroid patients and 30 healthy controls of age between 18 to 50 years of either sex were included in our study. Clinical criteria and biochemical tests were registered, and spirometry was done. Results Approximately 17% of the hypothyroid patients were normal, whereas 33% had mild restrictive lung impairment and the rest 50% had moderate to severe restrictive impairment on spirometry. Conclusion On comparing the hypothyroid patients with normal healthy person of same age group through spirometer, the ventilatory functions were diminished and these pulmonary functions improved after levothyroxine therapy for 6 months but could not reach the normal healthy values. A spirometric evaluation should be considered in hypothyroid patients, even in the absence of respiratory illness.

Vitamin D deficiency, impaired lung function and total and respiratory mortality in a cohort of older men: cross-sectional and prospective findings from The British Regional Heart Study

ObjectivesVitamin D deficiency is associated with chronic obstructive pulmonary disease (COPD). We examined the cross-sectional association between 25-hydroxyvitamin D (25(OH)D) and lung function impairment and assessed whether vitamin D deficiency...

Serum intracellular adhesion molecule-1 and interleukin-8 as predictors of pulmonary impairment among workers in secondary copper smelters

Copper smelter workers are exposed to harmful chemical agents in dust and fumes which contain harmful metals such as copper and arsenic. These substances are known to be respiratory irritants. This study aimed at investigating the effect of occupational exposure to copper and arsenic on the respiratory system. A group of 75 male exposed workers, and 75 male administrative employees (control group) were recruited from a secondary copper smelting factory. Full history, complete clinical examination, ventilatory function parameters (FVC, FEV1, FVC/FEV1 and FEF), and chest X-ray were done for both groups. Serum levels of ICAM-1 and IL8 (as markers of epithelial injury) were measured by ELISA. Serum copper and arsenic were measured by atomic absorption spectrophotometer. The exposed group was associated with increased respiratory symptoms, higher serum copper, arsenic, and ICAM-1and Il-8 as compared to the control group. There was a significant decrease in ventilatory parameters among the exposed group: 58.7% of the exposed group had restrictive lung impairment, 40% had obstructive impairment. In the exposed group a positive correlation between serum copper, arsenic and serum ICAM and IL8 was found. While a negative correlation was observed between both serum ICAM, IL8 and ventilatory parameters among the exposed group. Moreover, 36% of the exposed group had radiological infiltrates on chest X.ray. Occupational exposure to copper and arsenic was associated with ventilatory and radiological impairment, with a corresponding increase in the serum level of ICAM-1 and IL8, which can be used as biomarkers for pulmonary impairment among copper smelter workers.

Health impact assessment of auto rickshaw and cab drivers due to exposure to vehicular pollution in Delhi: an integrated approach.

Vehicular emission is an important contributor to air pollution in the urban environment and impacts the health of commuters as well as drivers. The in-vehicle concentration of pollutants is known to be higher than the ambient environment and varies with the mode of transport. Thus, this study attempts to assess the health impacts of air pollution exposure on auto rickshaws and cab drivers. The study was conducted in Delhi using a triangular approach involving a health perception survey, lung function test and in-vehicle monitoring of particulate matter (PM1, PM2.5, PM10) concentration to assess the health impacts of air pollution on auto rickshaw and cab drivers. A total of 150 respondents (75 from each occupation) were surveyed, and spirometry was performed for 40 respondents (20 from each occupation). Binary logistic regression showed auto rickshaw drivers were exposed to significantly higher in-vehicle PM concentrations in summers and winters and, thus, had a significantly higher risk of developing respiratory, ophthalmic and dermatological health symptoms (p< 0.05 and relative risk >1). Pulmonary function test showed obstructive lung impairment was reported only among auto rickshaw drivers (6%) and restrictive lung impairment was also more prevalent among auto rickshaw drivers (48%) than cab drivers (33%), suggesting a greater vulnerability of auto rickshaw drivers to respiratory health issues. Lung function impairment was associated with age (p= 0.002). The health and well-being of individuals is a matter of global concern, also highlighted in sustainable development goal no. 3. However, it was observed that neither auto rickshaw drivers nor cab drivers used formal/standard protective measures mainly due to unawareness or unaffordability. The study suggests increasing awareness and formulating guidelines to highlight the use of proper protective measures by these vulnerable groups and specific policy measures to protect outdoor workers like auto rickshaw drivers.

The Long-Term Impact of COVID-19 Pneumonia on the Pulmonary Function of Survivors.

BackgroundThe sequelae of COVID-19 pneumonia on pulmonary function and airways inflammation are still an area of active research.ObjectiveThis research aimed to explore the long-term impact of COVID-19 pneumonia on the lung function after three months from recovery.MethodsFifty subjects (age 18–60 years) were recruited and classified into two groups: the control group (30 subjects) and the post-COVID-19 pneumonia group (20 patients). Pulmonary function tests, spirometry, body plethysmography [lung volumes and airway resistance (Raw)], diffusion capacity for carbon monoxide (DLCO), and fractional exhaled nitric oxide (FeNO), were measured after at least 3 months post-recovery.ResultsSignificant reduction in total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume (FEV1), FEV1/FEV, and diffusing capacity for carbon monoxide (DLCO) was observed in post-COVID-19 subjects compared to controls. Restrictive lung impairment was observed in 50% of post-COVID-19 cases (n = 10) compared to 20% in the control group (n = 6, P = 0.026). In addition, mild diffusion defect was detected in 35% (n = 7) of the post-COVID-19 group compared to 23.3% (n = 7) in the controls (P = 0.012).ConclusionCOVID-19 pneumonia has an impact on the lung functions in terms of restrictive lung impairment and mild diffusion defect after three months from recovery. Therefore, a long-term follow-up of the lung function in post-COVID-19 survivors is recommended.

Lung function impairment and cardiometabolic risks among rural adults: implication for an aging society

BackgroundEarly detection and prevention of cardiometabolic risk factors in an increasingly aging society are a global public health concern. Maintaining adequate lung function is important for healthy aging. Few studies exist on lung function impairment and decline in primary healthcare settings, especially among rural adults with cardiometabolic risks. This study aimed to explore the prevalence of impaired lung function and its association with cardiometabolic risks among rural adults.MethodsA community-based, cross-sectional study was conducted between March and December 2019 in western coastal Yunlin County, Taiwan. The lung function test was measured by spirometry, based on the American Thoracic Society recommendations. Three lung function parameters were obstructive lung impairment, restrictive lung impairment, and mixed lung impairment. Restrictive, obstructive, and mixed type lung function was categorized as impaired. Cardiometabolic risk factors and metabolic syndrome were based on the national standard and include five abnormal biomarkers, including abdominal obesity, blood pressure, fasting plasma glucose, triglycerides, and decreased high-density cholesterol levels.ResultsThe median age of the 1653 (92.9%) participants with complete data was 66 years (interquartile range: 55 to 75 years). The prevalence of impaired lung function was 37%, including 31.7% restrictive, 2.5% obstructive, and 2.7% mixed type. Adults with impaired lung function (86% restrictive type) engaged more in smoking and betel nut chewing, ate fewer vegetables and fruit, and drank less water compared to the normal lung function group. After adjusting for potential confounding variables, multivariate logistic regression analysis showed that cardiometabolic risk factors were independently associated with restrictive lung impairment, while cigarette smoking (OR = 2.27, 95% CI = 1.14–4.53) and betel nut chewing (OR = 2.33, 95% CI = 1.09–5.01) were significantly associated with the obstructive type of lung impairment.ConclusionsA high prevalence of restrictive lung impairment, cardiometabolic risks, and unhealthy lifestyles among rural adults were found in this study. For adults with cardiometabolic risks in rural areas, initiating lifestyle modifications with culture-tailored programs to improve lung function should be an important issue for clinicians and primary healthcare providers.

Decreased quality of life and spirometric alterations even after mild-moderate COVID-19

BackgroundThe follow-up of recovered COVID-19 patients is still limited. We aimed to evaluate the changes in quality-of-life (QOL) and spirometric alterations in the convalescent phase of 115 patients with at least 30 days post-COVID-19. MethodsWe included patients with confirmed COVID-19 infection, available past medical records and at least 30 days after the onset of symptoms. All patients were asked to rate their general health condition before and after COVID-19 using the EQ-5D-5L standardized questionary and perform a spirometry at evaluation. ResultsIn this study, that included 70%(81/115) of patients with mild or moderate COVID-19; there was a severe decrease in QOL up to 56%(64/115). Alterations in usual activities and anxiety/depression were present in 59% of patients with a severe decrease in QOL. The persistence of symptoms was present in 63%(72/115). Restrictive lung impairment was the most common spirometric alteration in 17%(20/115), of whom 65%(13/20) had mild COVID-19. ConclusionsSpirometric alterations are presented even in mild COVID-19, and more remarkably, there is a high rate of alterations in quality of life after the recovery of this disease.

Waist to Height Ratio and Metabolic Syndrome as lung dysfunction predictors

Metabolic Syndrome (MetS) has been related to pulmonary diseases but its relationship with lung age has not been sufficiently studied. In addition, anthropometric variables have been associated with pulmonary dysfunction, highlighting the waist-to-height ratio (WHtR). The aim was to evaluate the relationship between MetS and: lung age, anthropometric variables and the alteration of lung function. A cross-sectional study was carried out in 1901 workers, evaluating lung function through lung age (Morris & Temple equation) and spirometric values. The diagnosis of MetS was based on the harmonized criteria. We measured anthropometric variables (WHtR, waist circumference, body mass index, waist to hip ratio), blood pressure and biochemical variables (glucose, cholesterol total, HDL, triglycerides). Workers suffering from MetS showed an accelerated lung aging (59.4 ± 18.7 years vs 49 ± 18.4 years). The WHtR ≥ 0.55 was significantly related to an increase in lung age (β = 6.393, p < 0.001). In addition, a significant linear trend was found between clinical categories of WHtR and lung dysfunction, restrictive and mixed pattern. MetS caused an accelerated lung aging and favored the presence of restrictive lung impairment. In addition, WHtR ≥ 0.55 has been shown as the best predictor for pulmonary health.

Lung function evaluation in heart failure: possible pitfalls.

Close to acute heart failure, a restrictive and/or obstructive lung impairment can be detected in the absence of any primitive lung disease. To avoid diagnostic pitfalls, lung function evaluation should be delayed until after full patient recovery. http://bit.ly/3aEy8ed

An SFTPC BRICHOS mutant links epithelial ER stress and spontaneous lung fibrosis.

Alveolar type 2 (AT2) cell endoplasmic reticulum (ER) stress is a prominent feature in adult and pediatric interstitial lung disease (ILD and ChILD), but in vivo models linking AT2 cell ER stress to ILD have been elusive. Based on a clinical ChILD case, we identified a critical cysteine residue in the surfactant protein C gene (SFTPC) BRICHOS domain whose mutation induced ER stress in vitro. To model this in vivo, we generated a knockin mouse model expressing a cysteine-to-glycine substitution at codon 121 (C121G) in the Sftpc gene. SftpcC121G expression during fetal development resulted in a toxic gain-of-function causing fatal postnatal respiratory failure from disrupted lung morphogenesis. Induced SftpcC121G expression in adult mice resulted in an ER-retained pro-protein causing AT2 cell ER stress. SftpcC121G AT2 cells were a source of cytokines expressed in concert with development of polycellular alveolitis. These cytokines were subsequently found in a high-dimensional proteomic screen of bronchoalveolar lavage fluid from ChILD patients with the same class of SFTPC mutations. Following alveolitis resolution, SftpcC121G mice developed spontaneous pulmonary fibrosis and restrictive lung impairment. This model provides proof of concept linking AT2 cell ER stress to fibrotic lung disease coupled with translationally relevant biomarkers.

A Study of Pulmonary Function Test in Type II Diabetes Mellitus-Spirometry Based

A Study of Pulmonary Function Test in Type II Diabetes Mellitus-Spirometry Based

Age at menarche and lung function: a Mendelian randomization study

A trend towards earlier menarche in women has been associated with childhood factors (e.g. obesity) and hypothesised environmental exposures (e.g. endocrine disruptors present in household products). Observational evidence has shown detrimental effects of early menarche on various health outcomes including adult lung function, but these might represent spurious associations due to confounding. To address this we used Mendelian randomization where genetic variants are used as proxies for age at menarche, since genetic associations are not affected by classical confounding. We estimated the effects of age at menarche on forced vital capacity (FVC), a proxy for restrictive lung impairment, and ratio of forced expiratory volume in one second to FVC (FEV1/FVC), a measure of airway obstruction, in both adulthood and adolescence. We derived SNP-age at menarche association estimates for 122 variants from a published genome-wide meta-analysis (N = 182,416), with SNP-lung function estimates obtained by meta-analysing three studies of adult women (N = 46,944) and two of adolescent girls (N = 3025). We investigated the impact of departures from the assumption of no pleiotropy through sensitivity analyses. In adult women, in line with previous evidence, we found an effect on restrictive lung impairment with a 24.8 mL increase in FVC per year increase in age at menarche (95% CI 1.8–47.9; p = 0.035); evidence was stronger after excluding potential pleiotropic variants (43.6 mL; 17.2–69.9; p = 0.001). In adolescent girls we found an opposite effect (−56.5 mL; −108.3 to −4.7; p = 0.033), suggesting that the detrimental effect in adulthood may be preceded by a short-term post-pubertal benefit. Our secondary analyses showing results in the same direction in men and boys, in whom age at menarche SNPs have also shown association with sexual development, suggest a role for pubertal timing in general rather than menarche specifically. We found no effect on airway obstruction (FEV1/FVC).

Change in prevalence of restrictive lung impairment in the U.S. population and associated risk factors: the National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 2007-2010.

BackgroundData for the U.S adult population from the National Health and Nutrition Examination Survey (NHANES) were used to evaluate risk factors for a restrictive pattern on spirometry and estimate the change in its prevalence from the 1988–1994 to 2007–2010 sampling periods. Several previous epidemiologic studies used the Global Initiative for Chronic Obstructive Lung Disease fixed forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 0.70 criteria for classifying restrictive pattern rather than the age-defined American Thoracic Society (ATS)/European Respiratory Society (ERS) lower limit of normal (LLN) criteria, which may lead to misclassification.MethodsSpirometry measurements from NHANES data for the 1988–1994 and 2007–2010 periods were analyzed to estimate the age-standardized prevalence of a restrictive pattern on spirometry and the change in prevalence over time for adults aged 20–79. A restrictive pattern was defined based on ATS/ERS LLN criteria as FEV1/FVC > LLN and FVC < LLN, and a moderate to more severe restrictive pattern was further evaluated using FEV1 < 70% predicted. The associations between demographic and other individual risk factors for restrictive lung impairment were examined using multivariable logistic regression models for the two consecutive time periods.ResultsThe overall age-standardized prevalence of restrictive pattern decreased significantly from 7.2% (1988–1994) to 5.4% (2007–2010) (p = 0.0013). The prevalence of moderate to more severe restrictive pattern also decreased significantly from 2.0% to 1.4% (p = 0.023). Factors positively associated with restrictive pattern on spirometry included age, female sex, white race, lower education, former and current smoking, and comorbidities including doctor-diagnosed cardiovascular disease, doctor-diagnosed diabetes, and abdominal obesity.ConclusionsThe overall prevalence of restrictive pattern and moderate to more severe restrictive pattern decreased between the 1988–1994 and 2007–2010 survey periods despite a population increase in the proportion of comorbidities associated with restrictive pattern (i.e. diabetes and abdominal obesity). This suggests a decline in individual risk factors for restrictive pattern and a need for future research.

Change in prevalence of restrictive lung impairment in the U.S. population and associated risk factors: the National Health and Nutrition Examination Survey (NHANES) 1988–1994 and 2007–2010

&#x0D; &#x0D; &#x0D; &#x0D; Background: Data for the U.S adult population from the National Health and Nutrition Examination Survey (NHANES) were used to evaluate risk factors for a restrictive pattern on spirometry and estimate the change in its prevalence from the 1988–1994 to 2007–2010 sampling periods. Several previous epidemiologic studies used the Global Initiative for Chronic Obstructive Lung Disease fixed forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) &gt; 0.70 criteria for classifying restrictive pattern rather than the age-defined American Thoracic Society (ATS)/European Respiratory Society (ERS) lower limit of normal (LLN) criteria, which may lead to misclassification.&#x0D; Methods: Spirometry measurements from NHANES data for the 1988–1994 and 2007–2010 periods were analyzed to estimate the age-standardized prevalence of a restrictive pattern on spirometry and the change in prevalence over time for adults aged 20–79. A restrictive pattern was defined based on ATS/ERS LLN criteria as FEV1/FVC &gt; LLN and FVC &lt; LLN, and a moderate to more severe restrictive pattern was further evaluated using FEV1 &lt; 70% predicted. The associations between demographic and other individual risk factors for restrictive lung impairment were examined using multivariable logistic regression models for the two consecutive time periods.&#x0D; Results: The overall age-standardized prevalence of restrictive pattern decreased significantly from 7.2% (1988–1994) to 5.4% (2007–2010) (p = 0.0013). The prevalence of moderate to more severe restrictive pattern also decreased significantly from 2.0% to 1.4% (p = 0.023). Factors positively associated with restrictive pattern on spirometry included age, female sex, white race, lower education, former and current smoking, and comorbidities including doctor-diagnosed cardiovascular disease, doctor-diagnosed diabetes, and abdominal obesity.&#x0D; Conclusions: The overall prevalence of restrictive pattern and moderate to more severe restrictive pattern decreased between the 1988–1994 and 2007–2010 survey periods despite a population increase in the proportion of comorbidities associated with restrictive pattern (i.e. diabetes and abdominal obesity). This suggests a decline in individual risk factors for restrictive pattern and a need for future research.&#x0D; &#x0D; &#x0D; &#x0D;

Assessment of Functional Lung Impairment in Hypothyroidism

Aims: To determine any functional lung impairment amongst patients diagnosed with hypothyroidism by spirometry. Methods: 21 hypothyroid subjects with TSH ≥10 mIU/L aged between 18-52 yrs were studied along with 21 healthy controls in the department of Physiology, Regional Institute of Medical Sciences (RIMS), Imphal. Hypothyroid subjects with other conditions/diseases which affect PFT were excluded. Spirometric parameters were conducted by means of computerised spirometer HELIOS 401/701(RMS, Chandigarh).The spirometric parameters studied are FVC, FEV1, FEV1/FVC, FEF25-75%, PEFR. Unpaired T-test and Pearson correlation was used and P value <0.05 was taken as significance. Result: Hypothyroid subjects showed a reduction of the % predicted value of FVC, FEV1, FEF25-75%, PEFR as compared to control subjects even though these values are within the normal values for their age, sex and gender. But the difference is statistically significant only for FVC. And the % predicted value for FEV1/FVC of hypothyroid subjects is found to be significantly increased than the controls. On analyzing and classifying only the hypothyroid subjects based on FVC values, 47% of the hypothyroid subjects were normal while 9% had mild restrictive lung impairment and the rest 43% had moderate to severe restrictive impairment. A negative correlation was found between TSH levels with the spirometric parameters FVC, FEV₁, FEV1/FVC and a positive correlation was found between T4 levels with FVC, FEV₁, FEV1/FVC. But none of the findings were not statistically significant. Conclusion: The pulmonary functions can be affected in hypothyroidism and they show a restrictive pattern of lung impairment.

Unraveling restrictive chronic lung disease in sickle cell disease [Editorial

A LEADING CAUSE of decreased life expectancy in adults with sickle cell disease (SCD) is acute and chronic lung disease (CLD). CLD historically encompassed both pulmonary f brosis and pulmonary hypertension;1 however, we now understand that these are distinct entities that may not necessarily coexist in SCD patients. While the latter has been the subject of thorough investigations that have determined its high prevalence (approximately 10% by right heart catheterization), strong association with chronic hemolytic anemia, and its relevance as a risk factor for early mortality in SCD,2–5 the former has not been studied comprehensively in the modern era. Pulmonary fibrosis is associated with restrictive lung defects on spirometric evaluation. This is a common finding in adult SCD patients, probably as a result of longstanding chronic inflammation of the small airways from recurrent acute chest syndrome (ACS), infections, vascular infarction and extra-pulmonary restriction.1,6 Longitudinal changes in lung function have also recently been described in children with SCD, with a study reporting an average loss of approximately 3% of forced expiratory volume in one second per year.7,8 Few studies have addressed the pulmonary complications of SCD in sub-Saharan Africa. This is a major area of unmet need, as children with SCD in sub-Saharan Africa are exposed to high rates of pulmonary infectious co-morbidities— predominantly tuberculosis and HIV—expected to exacerbate CLD.9 The article by Cook et al. in this issue of the Journal has focused on determining lung function abnormalities and symptoms of asthma in a cohort of 25 Malawian children with SCD and comparing it to local and international reference ranges.10 The authors reported spirometric abnormalities suggestive of restrictive rather than obstructive defects and the prevalence of wheeze to be comparable to a cohort of children without SCD from urban areas. This is surprising given the high prevalence of obstructive lung disease in areas with high household pollution from burning biomass fuel, such as many urban and rural areas in Malawi.11 Cook et al. hypothesize that in the Malawian SCD population, progression to late stage restrictive lung disease may be occurring earlier and more rapidly with various environmental influences acting as disease modifiers. The authors did not report on history of ACS in the study cohort, but it is possible that an increased number of episodes of ACS might be an important predictor of development of restrictive lung disease at an earlier age. In addition, the small sample size greatly limits the analysis of associated co-morbidities. Despite these limitations, this study provides a useful snapshot of the prevalence of pulmonary function testing abnormalities in an international cohort of pediatric SCD patients. Moreover, it offers the potential to spur further research to develop preventive and therapeutic strategies to alter the pattern of CLD over a larger and varied SCD cohort followed longitudinally. As acknowledged by the authors, a more accurate determination of lung function by provocation testing might be helpful in detecting transient obstructive or even mixed obstructive/restrictive defects. Such studies are required, as asthma has been identified as a significant co-morbidity in SCD and there is growing evidence that a history of ACS in SCD children is a risk factor for reactive airway disease and airway hyper-responsiveness after provocation challenge testing.12–14 Although these are studies of associations and they do not establish causality, asthma exacerbations may precipitate vaso-occlusion and ACS by inducing ventilation-perfusion mismatches.15 In conclusion, this study highlights the importance of restrictive lung impairment in SCD patients, but leaves critical questions unanswered regarding the causes and co-morbidities of interstitial lung disease, as well as the prevalence and role of asthma in SCD outcomes in SCD patients.

Airway pressure release ventilation as a therapeutic approach in a patient with severe obesity hypoventilation syndrome and restrictive lung impairment

Airway pressure release ventilation as a therapeutic approach in a patient with severe obesity hypoventilation syndrome and restrictive lung impairment

Phenotype characterization in patients with dynamin 2 related centronuclear myopathy

Background: Autosomal-dominant centronuclear myopathy (CNM) due to mutations in the dynamin 2 gene (DNM2) is a rare congenital myopathy characterized by generalized, slowly progressive muscle weakness and wasting usually beginning in late childhood or early adolescence. Methods: We screened 1582 consecutive muscle biopsies of adult patients (age ≥18 years) for morphologically characteristic signs of CNM. Patients with signs of CNM were screened for mutations in DNM2. We analysed clinical data and complementary neurophysiologic, respiratory, cardiac and muscle MRI data in these patients. Results: The age at biopsy was 39.3 years. 4 patients had histopathological signs of CNM (0.25%), 3 had the heterozygous mutation c.C1393T (p.R465W) in exon 11 in the middle domain of DNM2. In one patient mutational screening in DNM2, BIN1, MTM1, and RYR1was negative. In addition to the patients identified by the biopsy screening we were able to include two more patients (siblings) carrying the heterozygous mutation c.G1102A (p.E368K) in exon 8 in the middle domain of DNM2. The onset was neonatal and in infancy in the siblings and in childhood in further 3 patients. In one patient ptosis seemed to be present since adolescence but limb weakness began only at the age of 49 years. Facial abnormalities were common (n=6, facial weakness, n=3 bilateral ptosis, n=2 ophthalmoplegia). Weakness and wasting involved axial, proximal and distal muscles. In 3 patients distal muscles were more affected that proximal muscles. Two patients became wheelchair bound in their early adulthood. All patients had weak to absent deep tendon reflexes. Neurography suggested mild axonal neuropathy in two patients. 5 patients had a mild to moderate restrictive ventilatory defect. Contractures were an early sign (n=3 Achilles tendon, n=1 muscular torticollis, n=2 masticatory muscles. The clinical phenotype of the three patients with p.R465W mutation is rather mild. Conclusions: The phenotype in DNM2-CNM cases seems to be broader and includes more often patients with neonatal onset, axonal neuropathy, and unusual contractures as torticollis and restricted jaw opening than previously suggested. Restrictive lung impairment seems to be common in CNM and should be monitored regularly.

High-Resolution CT Findings of Parenchymal Fibrosis Correlate With Prognosis in Hypersensitivity Pneumonitis*

Histopathologic evidence of fibrosis on surgical lung biopsy has been associated with reduced survival in patients with hypersensitivity pneumonitis (HP). Changes of pulmonary fibrosis detected on CT may also correlate with prognosis in patients with HP. We identified 69 consecutive patients with HP diagnosed between January 1997 and December 2002 at Mayo Clinic, Rochester, MN. Patients were stratified into fibrotic and nonfibrotic groups based on the CT findings. Fibrosis was defined by the presence of irregular linear opacities, traction bronchiectasis, or honeycombing. Of 69 patients, 26 were classified as fibrotic and 43 as nonfibrotic. Patients in the fibrotic group were older, had longer symptom duration, were more likely to have crackles on auscultation, more likely to be exposed to avian antigen, and had greater restrictive lung impairment (p<0.05 for all comparisons). There were 11 deaths in the fibrotic group and 1 death in the nonfibrotic group (p<0.0001). In the regression analysis, CT evidence of fibrosis, more severe pulmonary function abnormalities, and the presence of crackles on auscultation were predictive of reduced survival (p<0.05 for all). The presence as well as the extent of fibrosis on CT was associated with increased mortality. The age-adjusted hazard ratio for mortality in patients with fibrosis was 4.6 (95% confidence interval, 2.0 to 20.1; p<0.0001). CT findings of parenchymal fibrosis are associated with reduced survival in patients with HP and may serve as a useful prognostic indicator.