LATE-BREAKING ABSTRACT: Artificial intelligence to improve the diagnostic power of complete pulmonary function tests

BackgroundIn patients with chronic obstructive pulmonary disease (COPD), the independent contributions of individual lung function variables to outcomes may be lower when they are modelled together if they are collinear. In addition, lung volume measurements may not be necessary after spirometry data have been obtained. However, these hypotheses depend on whether forced vital capacity (FVC) can predict total lung capacity (TLC). Moreover, the definitions of hyperinflation and air trapping according to lung function variables overlap and need be clarified. Therefore, the aim of this study was to evaluate the relationships among various lung function parameters to elucidate these issues.MethodsDemographic data and 26 parameters of full lung function were measured in 94 men with COPD and analyzed using factor and correlation analyses.ResultsFactor analysis revealed five latent factors. Inspiratory capacity (IC)/TLC and residual volume (RV)/TLC were most strongly correlated with all other lung volumes. IC/TLC, RV/TLC, and functional residual capacity (FRC)/TLC were collinear and were potential markers of air trapping, whereas TLC%, FRC%, and RV% were collinear and were potential markers of hyperinflation. RV/TLC >0.4 (or IC/TLC <0.4) was comparable with the ratio of forced expiratory volume in one second (FEV1) and FVC <0.7. FVC% and FEV1% were poorly correlated with TLC%. The correlation study showed that TLC%, RV/TLC, and FEV1% could be used to represent individual latent factors for hyperinflation, air trapping, inspiration, expiration, and obstruction. Combined with diffusion capacity%, these four factors could be used to represent comprehensive lung function.ConclusionsThis study identified collinear relationships among individual lung function variables and thus selecting variables with close relationships for correlation studies should be performed with caution. This study also differentiated variables for air trapping and lung hyperinflation. Lung volume measurements are still required even when spirometry data are available. Four out of 26 lung function variables from individual latent factors could be used to concisely represent lung function.

Rationale A complete pulmonary function test (PFT) includes plethysmography and diffusion capacity testing, which are considered the reference measurements for assessing hyperinflation, gas trapping, and lung diffusing capacity. However, conducting full PFTs can be challenging due to the significant time and staff resources required, and can be difficult to access. In contrast, oscillometry is increasingly being used in daily clinical practice as a non-invasive method to characterize the mechanical properties of the respiratory system. Intra-breath oscillometry measurements have emerged as a highly sensitive technique through the detection of patterns which are not reflected by standard spectral analysis. The present study aimed to evaluate the capability of intra-breath oscillometry parameters and their correlations with hyperinflation, gas trapping, and lung diffusion capacity as an alternative to a full PFT. Methods Data from a cross-sectional observational study (ClinicalTrials.govNCT05913323), which included adult participants with spirometry-confirmed “mild” (GOLD 1) or “very severe” (GOLD 4) COPD, was used. Intra-breath oscillometry parameters, i.e., the mean difference in lung reactance between inspiration and expiration cycles (ΔXrs) and reactance-volume loop area (AXV), were calculated from testing performed at a frequency of 10 Hz. Each participant also underwent a full PFT, which included measurements of total lung capacity (TLC) as a marker of hyperinflation, the ratio of residual volume (RV) to TLC (RV/TLC) as a marker of gas trapping, and the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) as a marker of gas transfer. Spearman correlation analysis, adjusted for age, sex, and FEV1, was conducted to estimate the association between the intra-breath parameters and PFT measurements. Results In 17 participants, 9 had mild and 8 had very severe COPD. Of these participants, 52.94% were female, with mean age of 66.4±8.3 years, and mean FEV1 of 1.5L (57.84% predicted). The strongest correlation coefficient observed was between ΔXrs and RV/TLC (0.75 [0.46,0.9] p&amp;lt;0.001), while ΔXrs was inversely correlated with DLco (-0.72 [-0.84,-0.41] p&amp;lt;0.001). AXV showed a weaker correlation with RV/TLC (0.69 [0.38,0.85] p&amp;lt;0.001) and a weaker inverse correlation with DLco (-0.50 [-0.87,-0.01] p&amp;lt;0.001). The correlation coefficients of ΔXrs and AXV with TLC were less than 0.5 (see Figure 1). Conclusions These results confirm that intra-breath oscillometry parameters can potentially be used to assess gas trapping and gas transfer in patients with COPD, serving as a possible complement and/or alternative to full PFTs.

To the Editor: We thank Ms Kress for her letter to the editor and interest in our article “Respiratory Symptoms Necessitating Spirometry Among Soldiers With Iraq/Afghanistan War Lung Injury (IAW-LI)” (JOEM September 2011).1 In reply to her concerns about “questionable generalizability,” our VA patient population is, in fact, quite similar to the general soldier and veteran population that we would consider generalizing our results with respect to demographic, socioeconomic, and other factors, which could potentially modify the relationship between deployment and the frequency of symptoms requiring spirometry. We did indicate in the article that our finding that the respiratory symptom rate of 14% of soldiers deployed to Iraq and Afghanistan who were seen at the Northport Veterans Affairs Hospital, is very similar to the 14% rate of ALL active-duty US Army soldiers answering surveys for the Millennium Study on whether they have respiratory symptoms while stationed in Iraq.2 Both groups include a subset of (1) those without a prior diagnosis of asthma, (2) who were nonsmokers, (3) graduates of basic training, and (4) fit for active duty and deployment after clearance at Fort Hood, TX. We agree that there are differences in demographics among VA users and non-VA users in the pre-Iraq War 2004 study by other authors cited by Ms Kress; however, our cohort comprises military personnel with Long Island zip codes, a region of relative affluence.3 The reader is incorrect in stating that veterans in our study were living in New York City; our catchment area comprises Nassau and Suffolk Counties of Long Island. Northport is 46 miles from Manhattan. There are separate VA Medical Centers in Brooklyn, Manhattan, and the Bronx not included in the study. We disagree that these VA users in our study had poorer baseline health status compared with nonusers since all were (1) young, (2) healthy, (3) combat-ready graduates of basic training, and (4) deemed fit for deployment prior to their 12-month tour of duty. Rather than having a “lower socioeconomic status and overall poorer health status” as the reader suggests, our patients are self-selected young, healthy Long Island athletes from higher socioeconomic strata drawn to the rigors of military service. Although combat veterans may receive free medical care for any condition related to their service in the Iraq/Afghanistan theatre, first they must qualify for a compensation and pension (C&P) examination, which is conducted by limited numbers of members of the physician staff. Although it may be more likely that veterans deployed to Iraq and Afghanistan are more aware of benefits and may seek out the VA more often than those stationed elsewhere, however, the respiratory symptom rate is not only sevenfold higher among those deployed to Iraq/Afghanistan, but also the rate among stateside troops is extremely low at 1.8%, suggesting that it is an uncommon occurrence to have new-onset respiratory symptoms while stationed stateside. The process upon entering the Northport VA is to check-in with a survey in the Operation Iraqi Freedom/Operation Enduring Freedom/Operation New Dawn (OIF/OEF/OND) clinic. The patient is then assigned a primary care physician outside the OIF/OEF/OND clinic. More than 70% of patients who went to Iraq or Afghanistan in our study were seen in a pulmonary clinic. To get complete pulmonary function tests, a given patient must be seen in pulmonary clinic because only a pulmonary fellow or pulmonary attending can order body box plethysmography (complete pulmonary function tests), and these data are interpreted and signed by both the fellow and the pulmonary attending. We used the pulmonary fellow note to check the values of the scanned in PDF file of complete pulmonary function testing. If there was a standard interpretation of basic spirometry without numerical values, we did not include the patient. The reader says we “do not account for confounding for a variety of established risk factors for respiratory symptoms despite having adequate sample size for multivariable analysis.” We indeed did conduct a multivariable analysis in an earlier version of the article, adjusting for important covariates, such as age, gender, smoking. Even after adjusting for these confounders, smoking, gender, age, and so forth, the effect is still statistically significant though the effect size is slightly lower. Critically important is that there is a subset of nonsmoking soldiers with new-onset symptoms after deployment to Iraq/Afghanistan warranting treatment with medications. The role of smoking as a covariate is complicated, in that it is likely both a confounder and an intermediate in the causal pathway between deployment and incidence of respiratory symptoms. Smoking behaviors change during deployment (increasing in prevalence and intensity, on average). Anecdotally, we understand that many soldiers only smoke while deployed, and many who continue to smoke subsequent to their deployment reduce their cigarette consumption. We are fortunate to have data on smoking status to be able to adjust for confounding by smoking. However, we are not able to distinguish between smoking prior to deployment and during deployment. As such, the analysis, which includes smoking as a covariate, provides an estimate of the effect of deployment on symptoms/spirometry independent of the deployment-smoking-respiratory symptom pathway. Similarly, traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are intermediates in the causal pathway and are not confounders. Deployment increases the risk of TBI and PTSD, which may lead to respiratory symptoms, since blast overpressure associated with TBI is also associated with lung injury, and PTSD is a risk factor for asthma. We reported very high rates of traumatic brain injury in the article. Surveillance bias is suggested by the reader on the basis of the assumption that health care providers are likely to request additional tests. Referring physicians are licensed physicians and faculty members at Stony Brook University who order tests as they deem necessary. They do not have financial incentives to order more tests. Both groups—Iraq/Afghanistan deployed and those deployed elsewhere—have lung function deficits. We agree with the reader that well-designed, prospective cohort studies of deployment-associated chronic respiratory symptoms and diseases are warranted. Regarding the semantics of lung injury, we note these are previously healthy soldiers without asthma and with athletic performance at the level of basic training, including the ability to run 2 miles. We coined the term of this new-onset clinical syndrome Iraq Afghanistan War lung injury (IAW-LI) because this was particular to deployment, analogous to the initial reports of “World Trade Center Cough.” New-onset respiratory health problems are not limited to those on Long Island. In a recent New England Journal of Medicine article, King et al4 recently published a case series of symptomatic post-Iraq deployment troops from Fort Campbell Kentucky who had constrictive bronchiolitis despite all subjects having normal spirometry. We believe that the rate of lung disease is under-diagnosed in our population because the Northport VA does not have on-site sophisticated testing such as impulse oscillometry, methacholine challenge, cardiopulmonary exercise testing with pre- and postspirometry, exhaustive aeroallergen testing including regional aeroallergens from Iraq and Afghanistan, which may cross-react with antigens in America, and, most importantly, only one soldier has had an open lung biopsy (and was not included in this study), so we would have missed all cases of constrictive bronchiolitis and hypersensitivity pneumonitis in the study by King et al. We thank Ms Kress for interest in our article and the journal editors for the opportunity to clarify concepts. We look forward to conducting more research in this emerging field and reading the work of other investigators. Anthony M. Szema, MD, FCCP Walid Salihi, DO Stony Brook University School of Medicine & Medical Center Veterans Affairs Medical Center Northport, NY Khalil Savary, MD Jacobi Medical Center, Bronx, NY John J. Chen, PhD John A. Burns School of Medicine, University of Hawaii Manoa, Hawaii

Granulomatous-lymphocytic Interstitial Lung Disease in a Patient with Common Variable Immunodeficiency

New Findings What is the central question of this study? Are chronotropic responses to a 6‐minute walk test different in women with post‐acute coronavirus disease 2019 (COVID‐19) syndrome compared with control subjects? What is the main finding and its importance? Compared with control subjects, the increase in heart rate was attenuated and recovery delayed after a 6‐minute walk test in participants after infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Women reporting specific symptoms at time of testing had greater impairments compared with control subjects and SARS‐CoV‐2 participants not actively experiencing these symptoms. Such alterations have potential to constrain not only exercise tolerance but also participation in free‐living physical activity in women during post‐acute recovery from COVID‐19. The short‐term cardiopulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are well defined. However, the implications of cardiopulmonary sequelae, persisting beyond acute illness, on physical function are largely unknown. Herein, we characterized heart rate responses to and recovery from a 6‐minute walk test (6MWT) in women ∼3 months after mild‐to‐moderate SARS‐CoV‐2 infection compared with non‐infected control subjects. Forty‐five women (n = 29 SARS‐CoV‐2; n = 16 controls; age = 56 ± 11 years; body mass index = 25.8 ± 6.0 kg/m2) completed pulmonary function testing and a 6MWT. The SARS‐CoV‐2 participants demonstrated reduced total lung capacity (84 ± 8 vs. 93 ± 13%; P = 0.006), vital capacity (87 ± 10 vs. 93 ± 10%; P = 0.040), functional residual capacity (75 ± 16 vs. 88 ± 16%; P = 0.006) and residual volume (76 ± 18 vs. 93 ± 22%; P = 0.001) compared with control subjects. No between‐group differences were observed in 6MWT distance (P = 0.194); however, the increase in heart rate with exertion was attenuated among SARS‐CoV‐2 participants compared with control subjects (+52 ± 20 vs. +65 ± 18 beats/min; P = 0.029). The decrease in heart rate was also delayed for minutes 1–5 of recovery among SARS‐CoV‐2 participants (all P < 0.05). Women reporting specific symptoms at the time of testing had greater impairments compared with control subjects and SARS‐CoV‐2 participants not actively experiencing these symptoms. Our findings provide evidence for marked differences in chronotropic responses to and recovery from a 6MWT in women several months after acute SARS‐CoV‐2 infection.

The thoraco-lumbar bracing is an effective management of adolescent idiopathic scoliosis (AIS). Studies have shown that brace wearing reduces lung volume. Whether or not the Sforzesco brace, frequently used in Italy, affects lung volume has not been investigated. We studied the immediate effect of Sforzesco bracing on lung volumes in 11 AIS patients (10 F, 1 M; aged 13.6 ± 1.6 yrs) mean Cobb angle 26 ± 4.49 degrees. Lung function variables and the perceived respiratory effort were recorded twice, before and 5 min after bracing. The one-way analysis of variance repeated measures, and multiple comparison tests, showed that means of unbraced variables were not significantly different from the corresponding means of predicted values, whereas means under brace were significantly lower (p < 0.05) compared to both predicted and baseline values of respiratory variables. In addition, a significant correlation (p < 0.0001) was found between unbraced and braced values, and linear regression equations were calculated. A significant but clinically unimportant increase in perceived effort was observed under the brace. In conclusion, data indicate that lung function is not impaired in moderate AIS and that wearing the Sforzesco brace causes an immediate, predictable reduction of lung volumes. Data also suggest that the respiratory discomfort during brace wearing could not be due to respiratory function defects.

Lung function and chest radiographs were reviewed in 357 coalworkers who had been referred from the Cardiff Pneumoconiosis Medical Panel. The chest films were read according to the 1980 ILO classification of radiographs by three experienced readers. An irregularity score, reflecting the shape of the small opacities, was derived from the readings and compared with the lung function variables. Men with higher irregularity scores had significant reductions in ventilatory capacity and gas transfer factor, with no change in total lung capacity, after age, height, profusion of small opacities, and smoking habit had been taken into account. The effects were present both in those with and in those without large opacities. The agreement between readers over the shape of opacities was almost as good as for their profusion. Men with rounded opacities had a lower gas transfer factor if they were predominantly of the "p" type. The results are consistent with those for a combination of emphysema and interstitial fibrosis, which has been found in coalworkers with irregular opacities.

RATIONALE: Survivors of the first SARS epidemic had impaired exercise capacity and lung function remain at six months after illness.1 Due to the novel nature of SARS-CoV-2, practitioners can only extrapolate from prior coronavirus pandemics when anticipating sequelae of COVID-19. This study seeks to help draw conclusions about long-term outcome in survivors of COVID-19. METHODS: Patients over 18 with confirmed COVID-19 are prospectively enrolled to a registry which collects clinical, serologic, functional, and radiographic data at one month, three months, six months, and twelve months post recovery from acute infection, as determined by symptoms (outpatients) or hospital discharge (inpatients). Complete pulmonary function tests (PFT) and 6 minute walk distances (6MWD) are collected at each time point. RESULTS: All currently completed PFT and 6MWD data were included in analysis (PFT: 1 month, n=16;3 months, n=26;6 months, n=25;6MWD: 1 month, n=14;3 months, n= 17;6 months, n=21). Mean 6MWD was 350m at 1 month, 362m at 3 months, and 373m at 6 months. At 1 month, 56% had normal spirometry;38% had restriction and 6% had mixed obstructive/restrictive pattern. At 3 months, 50% had normal spirometry with 42% showing restriction, 4% obstruction, and 4% mixed pattern. By 6 months, 64% had normal spirometry, 24% had restriction, and 12% had obstruction. There was diffusion limitation in 50% at both 1 month and 3 months;by 6 months, this improved to 32%. At one month, subjects older than 65 had significantly lower DLCO when compared those younger than 40 (10.54 vs 24.07 ml/min/mmHg, p<0.001) and when compared those aged 40-64 (10.54 vs 18.58 ml/min/mmHg, p<0.01);this change persisted at six months (13.67 vs 20.7 ml/min/mmHg, p<0.05). When stratified by clinical illness severity, or weight, there was no significant difference seen across PFT variables. 6MWD did not show significant difference when stratified by age, weight, or illness severity. CONCLUSIONS: In survivors of COVID-19, there are persistent functional and clinical sequelae up to six months post-recovery. Functional capacity remains impaired at six months. Predominant spirometric abnormality is restriction, which improves over time. Importantly, DLCO remains low in half of the subjects at both one and three months, with some improvement by 6 months. The diffusion impairment is significantly worse in patients older than 65. More investigation is required to elucidate the etiology of ongoing diffusion limitation and correlate with ventilation/perfusion studies.

A few previous reports have shown that lung volumes, diffusion capacity as well as bronchial hyperresponsiveness (BHR) are increased in well trained swimmers as compared to other athletes and controls. It is unknown if this can be applied to elite athletes and if this is due to genetic or environmental factors such as the specificity of the swim training and the exposure to chlorine derivatives in the swimming pools. PURPOSE: To compare lung function, BHR and respiratory symptoms in elite swimmers and cross country skiers. METHODS: In a cross sectional study, 29 elite swimmers (17♂/12♀) aged 16–28 years and 30 elite cross-country skiers (20♂/10♀) aged 20–37 years, all competing at high international level, measured lung function by maximal expiratory flow volume loops, forced expiratory flow the first second (FEV1), forced vital capacity (FVC), forced expiratory flow at 50 % of FVC (FEF50) and bronchial hyperresponsiveness was measured by methacholine provocation test, provocation dose at 20 % reduction in FEV1 (PD20meth). Training time per week, symptoms and use of antiasthmatic medication were recorded with the AQUA-questionnaire and by a clinical examination. Antiasthmatic medication was withheld according to ERS guidelines. RESULTS: The elite swimmers had a significant higher FEV1, as compared to the cross country skiers, 4.73L (4.39, 5.07) mean (95 % confidence interval) vs 4.31L (4.06, 4.57) (p=0.05) respectively, FEV1 (% predicted), 114.7 % (110.2, 119.2) vs 103.0 % (99.2, 106.7) (p<0.001) respectively and FVC (% predicted), 122.4 % (116.9, 127.8) vs112.2 % (108.4, 115.9) (p=0.002) respectively. Twenty-three swimmers had a PD20meth ≤ 4 umol as compared to six cross country skiers. Mean training time per week was significant higher in swimmers, 23.8 hours (23.1, 24.4) vs 17.1 hours (16.6, 17.6) (p< 0.001). 27.6 % of the swimmers and 70 % of the skiers had an asthma diagnosis and 37.9 % of the swimmers and 83.3 % of the skiers used daily antiasthmatic medication. No differences were found in the other lung function variables or in self-reported symptoms. CONCLUSION: Elite swimmers have larger lung volumes and FEV1 than elite cross country skiers, but it seems that swimmers are more likely to develop severe BHR due to exposure to chlorine derivatives during their prolonged daily training sessions.

Reports show wide variability of electromyography (EMG) in detecting pediatric neuromuscular disorders. The study's aim was to determine EMG/nerve conduction study accuracy compared to muscle biopsy and final clinical diagnosis, and sensitivity for myopathic motor unit potential detection in childhood. Of 550 EMG/nerve conduction studies performed by the same examiner from a pediatric neuromuscular service, 27 children (ages 6 days to 16 years [10 boys; M:F, 1:1.7]) with muscle biopsies and final clinical diagnoses were compared retrospectively. Final clinical diagnoses were congenital myopathies (5 of 27,18%), nonspecific myopathies (biopsy myopathic, final diagnosis uncertain; 6 of 27, 22%), congenital myasthenic syndrome (3 of 27, 11%), juvenile myasthenia gravis (1 of 27, 4%), arthrogryposis multiplex congenita (2 of 27, 7%), hereditary motor and sensory neuropathy (1 of 27, 4%), bilateral peroneal neuropathies (1 of 27, 4%), and normal (8 of 27, 30%). There were no muscular dystrophy or spinal muscular atrophy patients. EMG/nerve conduction studies had a 74% agreement with final clinical diagnoses and 100% agreement in neurogenic, neuromuscular junction, and normal categories. Muscle biopsies concurred with final diagnoses in 87%, and 100% in myopathic and normal categories. In congenital myasthenic syndrome, muscle biopsies showed mild variation in fiber size in 2 of 3 children and were normal in 1 of 3. EMG sensitivity for detecting myopathic motor unit potentials in myopathies was 4 of 11 (36%), greater over 2 years of age (3 of 4, 75%), compared to infants less than 2 years (1 of 7, 14%), not statistically significant (P = .0879). EMGs false-negative for myopathy in infants < 2 years of age were frequently neurogenic (3 of 6, 50%). In congenital myopathies EMG detected myopathic motor unit potentials in 40%, with false-negative results neurogenic (20%) or normal (40%). Because our study has no additional tests for active myopathies, for example Duchenne muscular dystrophy genetic testing, our sensitivity for myopathies is lower than if we used a more global view. In conclusion, EMG detection rate of myopathic motor unit potentials at a young age was low, improving in children over 2 years of age. In neurogenic and neuromuscular junction disorders, the EMG has a very high detection rate. In children with mild to moderate neurogenic EMG findings and normal nerve conduction, a myopathy should always be considered.

A homogeneous population of 42 women with idiopathic scoliosis (mean age, 20.8 years and mean major thoracic curve of 58.2 degrees) had a complete pulmonary function test (PFT) at rest before, and a minimum of 3 years after, spinal fusion (mean, 7.7 years) to evaluate the effect of scoliosis and its surgical correction on PFT at rest. A multifactorial analysis showed that only the vital capacity (VC) was significantly lowered to 81% of predicted value (P less than 0.05). All of the other parameters of pulmonary volumes, flow, and gas exchanges, where corrected for the loss of lung volume, were within normal limits, showing pure restrictive changes in this population. Double-major curves were more severe, but no significant difference in PFTs were found with single thoracic curves. Curves over 50 degrees had significantly lower VC. The surgical correction of 40% is permanent and the functional improvement in postoperative vital capacity (VC) of 12% is significant (P less than 0.05). Other factors, such as the time between the two evaluations, the age of the patient, pelvic obliquity, trunk imbalance, and degree of kyphosis did not have any correlation with the observed changed on any of the PFT results. Therefore, early correction by spinal fusion in idiopathic scoliosis brings on some improvement of the vital capacity at rest and may prevent deterioration with progression of the curve.

IMPULSE OSCILLOMETRY IDENTIFIES DISTINCT ASTHMA PHENOTYPES ON CLUSTER ANALYSIS

Background and purposePatients with neuromuscular conditions are at increased risk of suffering perioperative complications related to anaesthesia. There is currently little specific anaesthetic guidance concerning these patients. Here, we present the European Neuromuscular Centre (ENMC) consensus statement on anaesthesia in patients with neuromuscular disorders as formulated during the 259th ENMC Workshop on Anaesthesia in Neuromuscular Disorders.MethodsInternational experts in the field of (paediatric) anaesthesia, neurology, and genetics were invited to participate in the ENMC workshop. A literature search was conducted in PubMed and Embase, the main findings of which were disseminated to the participants and presented during the workshop. Depending on specific expertise, participants presented the existing evidence and their expert opinion concerning anaesthetic management in six specific groups of myopathies and neuromuscular junction disorders. The consensus statement was prepared according to the AGREE II (Appraisal of Guidelines for Research & Evaluation) reporting checklist. The level of evidence has been adapted according to the SIGN (Scottish Intercollegiate Guidelines Network) grading system. The final consensus statement was subjected to a modified Delphi process.ResultsA set of general recommendations valid for the anaesthetic management of patients with neuromuscular disorders in general have been formulated. Specific recommendations were formulated for (i) neuromuscular junction disorders, (ii) muscle channelopathies (nondystrophic myotonia and periodic paralysis), (iii) myotonic dystrophy (types 1 and 2), (iv) muscular dystrophies, (v) congenital myopathies and congenital dystrophies, and (vi) mitochondrial and metabolic myopathies.ConclusionsThis ENMC consensus statement summarizes the most important considerations for planning and performing anaesthesia in patients with neuromuscular disorders.

Impaired development and reduced lung capacity are risk factors of asthma and chronic obstructive pulmonary disease. Previously, our genomewide linkage analysis of C3H/HeJ (C3H) and JF1/Msf (JF1) mouse strains identified quantitative trait loci (QTLs) associated with the complex traits of dead space volume (Vd), total lung capacity (TLC), lung compliance (CL), and diffusing capacity for CO (D(CO)). We assessed positional candidate genes by comparing C3H with JF1 lung transcript levels by microarray and by comparing C3H, BALB/cByJ, C57BL/6J, A/J, PWD/PhJ, and JF1 strains, using exon sequencing to predict protein structure. Microarray identified >900 transcripts differing in C3H and JF1 lungs related to lung development, function, and remodeling. Of these, three genes localized to QTLs associated with differences in lung function. C3H and JF1 strains differed in transcript and protein levels of superoxide dismutase 3, extracellular [SOD3; mouse chromosome (mCh) 5: VD] and transcript of trefoil factor 2 (TFF2; mCh 17: TLC and D(CO)), and ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2; mCh 15: TLC and CL). Nucleotide sequencing of Sod3, Tff2, and previously identified Relaxin 1 (Rln1; mCh 19: CL) uncovered polymorphisms that could lead to nonsynonymous amino acid changes and altered predicted protein structure. Gene-targeted Sod3(-/-) mice had increased conducting airway volume (Vd/TLC) compared with strain-matched control Sod3(+/+) mice, consistent with the QTL on mCh 5. Two novel genes (Tff2 and Enpp2) have been identified and two suspected genes (Sod3 and Rln1) have been supported as determinants of lung function in mice. Findings with gene-targeted mice suggest that SOD3 is a contributing factor defining the complex trait of conducting airway volume.

Expert Panel Report 3: Moving forward to improve asthma care