Burden, resilience and coping in caregivers of patients with interstitial lung disease.

RATIONALE: Prior work has described the experience of caregiving in idiopathic pulmonary fibrosis, but the effect on caregivers in interstitial lung disease (ILD) has not been explored. OBJECTIVES: Describe the burden, resilience, and health related quality of life (HRQoL) of caregivers of people with ILD. METHODS: In a mixed methods study, ILD caregivers completed questionnaires and participated in focus groups. A qualitative thematic analysis of the focus group transcripts was conducted. RESULTS: Thirty seven caregivers completed the survey, and 15 participated in the focus groups. 65% were female; the average age was 66 (SD = 13). The mean Short Form-36 role emotional and mental health scores were 18 (SD = 4) and 46 (SD = 7). The focus groups identified 4 major themes: emotional burden, changes in relationship, coping strategies, and unmet needs of caregivers. CONCLUSIONS: Caregiving for patients with ILD significantly impairs HRQoL, particularly, emotional health. Increasing resources could improve the caregiving experience in ILD.

Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis.

Some patients with idiopathic pulmonary fibrosis experience acute exacerbations in their respiratory status leading to substantial morbidity and mortality. Occult aspiration of gastric contents has been proposed as one possible mechanism leading to these acute exacerbations. We sought to determine whether pepsin, a marker of gastric aspiration, is elevated in bronchoalveolar lavage fluid obtained from patients during acute exacerbation of idiopathic pulmonary fibrosis, compared with that obtained in stable disease. Lavage samples were obtained in a case-control study of well-characterised patients. Acute exacerbation was defined using standard criteria. Levels of lavage pepsin were compared in cases and controls, and were correlated with clinical features and disease course. 24 cases with acute exacerbations and 30 stable controls were identified. There were no significant differences in baseline demographics between the two groups. Pepsin level was an indicator of acute exacerbation status (p=0.04). On average, pepsin appeared higher in patients with acute exacerbations compared with stable controls. This difference was driven by a subgroup of eight patients (33%) with pepsin levels ≥70 ng·mL(-1). Pepsin level was not an independent predictor of survival time. These results suggest occult aspiration may play a role in some cases of acute exacerbation of idiopathic pulmonary fibrosis.

Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease.

Interstitial lung disease is a common manifestation of rheumatoid arthritis; however, little is known about factors that influence its prognosis. The aim of the present study was to determine whether or not the usual interstitial pneumonia pattern found on high-resolution computed tomography (HRCT) is of prognostic significance in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Patients with RA-ILD were identified retrospectively (n = 82). The relationship of a definite usual interstitial pneumonia pattern on HRCT to survival was determined and compared to that in a cohort of patients with radiologically diagnosed idiopathic pulmonary fibrosis (n = 51). A definite usual interstitial pneumonia pattern was seen in 20 (24%) out of 82 patients with RA-ILD. These patients showed worse survival than those without this pattern (median survival 3.2 versus 6.6 yrs), and a similar survival to those with idiopathic pulmonary fibrosis. On multivariate analysis, a definite usual interstitial pneumonia pattern on HRCT was associated with worse survival (hazard ratio of 2.3). Analysis of specific HRCT features demonstrated that traction bronchiectasis and honeycomb fibrosis were associated with worse survival (hazard ratio of 2.6 and 2.1, respectively). Female sex (hazard ratio of 0.30) and a higher baseline diffusing capacity of the lung for carbon monoxide (hazard ratio of 0.96) were associated with better survival. A definite usual interstitial pneumonia pattern on HRCT has important prognostic implications in RA-ILD.

Organizing pneumonia and lymphoplasmacytic inflammation predict treatment response in idiopathic pulmonary fibrosis.

AIMS: To identify individual histopathological features within usual interstitial pneumonia pattern that predict responsiveness to immunosuppressive therapy. METHODS AND RESULTS: Fifty-six retrospectively confirmed usual interstitial pneumonia pattern surgical lung biopsy specimens from subjects with idiopathic pulmonary fibrosis treated with corticosteroid and cytotoxic therapy were included. Eleven prospectively defined histopathological features were evaluated by two expert pulmonary pathologists. Regression analysis identified predictors of response to therapy, as defined by the change in percent predicted forced vital capacity over 6 months. Additional end-points were change in dyspnoea score over 6 months, and survival time. Improvement in percent predicted forced vital capacity was associated with lymphoplasmacytic inflammation, while worsening of percent predicted forced vital capacity was associated with the presence of organizing pneumonia and fibroblast foci. Worsening dyspnoea was associated with fibroblast foci. Survival time was associated with age and baseline percent predicted forced vital capacity, but not with any individual histopathological feature. CONCLUSIONS: In pathological usual interstitial pneumonia pattern, the presence of lymphoplasmacytic inflammation predicts responsiveness to immunomodulatory therapy, while airspace organization predicts lack of response.

Neurofibromatosis-associated lung disease: a case series and literature review.

An association of neurofibromatosis with diffuse lung disease (NF-DLD) has been described, but its true prevalence and characteristics remain unclear. The objective of the present study was to define diffuse lung disease in patients with neurofibromatosis. A retrospective case series and literature review in a tertiary care academic medical centre is reported in which medical records, chest radiographs and high-resolution computed tomography (HRCT) scans were reviewed. A total of 55 adult patients with neurofibromatosis were identified, three of whom had NF-DLD. A literature review revealed 16 articles reporting 61 additional cases, yielding a total of 64 NF-DLD cases. The mean age of patients was 50 yrs. Males outnumbered females; most reported dyspnoea. Of the 16 subjects with documented smoking histories, 12 were ever-smokers. Eight patients had HRCT scan results demonstrating ground-glass opacities (37%), bibasilar reticular opacities (50%), bullae (50%), cysts (25%) and emphysema (25%); none had honeycombing. A group of 14 patients had surgical biopsy results that showed findings of interstitial fibrosis (100%) and interstitial inflammation (93%). In conclusion, neurofibromatosis with diffuse lung disease is a definable clinical entity, characterised by upper lobe cystic and bullous disease and lower lobe fibrosis. Its relationship to smoking remains unclear.

The clinical significance of histopathologic subgroups in idiopathic interstitial pneumonia: is surgical lung biopsy essential?

For many years, the clinical entity of idiopathic interstitial pneumonia (IIP) has been a source of confusion for physicians. There has been much debate over the utility of subclassifying this condition histopathologically. It now appears that such classification is useful, and the most important distinction is the presence or absence of usual interstitial pneumonia (UIP). Unlike the other histopathologic subgroups, UIP has a grave prognosis and responds poorly to traditional therapies. To emphasize this clinical difference, the diagnosis of idiopathic pulmonary fibrosis (IPF), once used synonymously with IIP, is now reserved for only those patients with the histopathologic pattern of UIP. Although the gold standard for the diagnosis of IPF/UIP remains surgical lung biopsy, recent studies suggest that careful clinical and radiographic evaluation can identify IPF/UIP with a specificity of 90% or more. In the absence of a clear clinical diagnosis, we recommend pursuing surgical lung biopsy. Knowledge of the underlying histopathology will allow for more accurate prognosis, help guide therapy, and make possible the clinical investigation of novel therapeutic agents for patients with IIP.

Possible extrathymic development of nonfunctional T cells in a patient with complete DiGeorge syndrome.

Complete DiGeorge syndrome is characterized by the clinical triad of cardiac malformation, hypocalcemia, and T cell immunodeficiency due to congenital athymia. We describe an infant with complete DiGeorge syndrome who at presentation had no circulating T cells detectable by flow cytometry. The patient spontaneously developed circulating T cells but these cells did not proliferate in response to mitogens. The T cell receptor Vbeta repertoire was severely restricted. All T cells were host, not maternal, as assessed by fluorescent in situ hybridization evaluation of 22q11 hemizygosity. At autopsy, this patient had no grossly detectable thymus tissue and no microscopic evidence for thymopoiesis. These findings suggest that appearance of T cells in infants with complete DiGeorge syndrome may represent oligoclonal expansions of a small number of T cells that may have matured extrathymically and which do not respond in vitro to mitogen stimulation.

Mutations in purine nucleoside phosphorylase deficiency.

Purine nucleoside phosphorylase deficiency is an inherited disease of purine metabolism characterized clinically as combined immunodeficiency. The molecular defects have been published for 4 different alleles in 3 patients. We report four new mutations including two amino acid substitutions, A174P and G190V, a single codon deletion, delta I129, and a point mutation in intron 3 which leads to aberrant splicing and creation of a premature stop codon in exon 4 (286-18G-->A). Of the previously reported mutations, E89K was found in one additional patient, and R234P was found in 3 unrelated patients, making R234P the most common mutation reported to date in this disease.

The role of N-linked carbohydrate residues in lymphokine-activated killer cell-mediated cytolysis.

We evaluated LAK cell cytotoxicity toward a sensitive B cell lymphoma and several resistant EBV-transformed cell lines in order to explore the mechanism by which some cells are preferentially recognized as targets. Cytolysis of the sensitive cells was inhibited by monoclonal antibodies against the surface proteins LFA-1 and ICAM-1; however, surface expression of ICAM-1 was similar on the resistant and sensitive cell lines. Prevention of post-translational addition of N-linked oligosaccharides by treatment of the resistant cells with tunicamycin resulted in a dramatic enhancement in LAK cell cytotoxicity which was partially inhibited by antibodies against LFA-1 and ICAM-1. Treatment of the resistant cells with the endoglycosidase N-glycanase also increased LAK cell sensitivity. Tunicamycin treatment caused a decrease in the molecular weight of ICAM-1 from approximately 95,000 to 50,000 Da. Conjugate formation between the LAK cells and the sensitive and resistant target cells was similar before and after deglycosylation. We conclude that carbohydrate modification of ICAM-1 or an alternative glycoprotein confers resistance to LAK cell cytotoxicity in some cell lines.

IgG1, IgG2 and IgM responses to two Haemophilus influenzae type b conjugate vaccines in young infants.

PRP-meningococcal outer membrane protein complex (PRP-OMPC) and oligosaccharide linked to variant diphtheria toxin (HbOC) Haemophilus influenzae type b (HIB) conjugate vaccines have both been licensed for United States infants at 2 months of age. Differences in serologic responses for these vaccines have been noted with PRP-OMPC producing an early response at 2 months of age and HbOC producing a higher response after a third dose at 6 months of age. To further characterize the nature of these distinct responses, we measured the IgG1, IgG2 and IgM anti-HIB concentrations by enzyme-linked immunosorbent assay after administration of both vaccines. PRP-OMPC produced an IgM and IgG1 anti-HIB response following the initial dose at 2 months of age. After two doses of HbOC an increase in IgG1 and IgM were noted and after a third dose at 6 months of age an IgG2 anti-HIB response occurred. In addition 33 study subjects were boosted with PRP-OMPC at age 18 months and compared with 34 subjects who received only a primary dose. The anti-HIB IgG1 and IgG2 concentrations following the booster dose were both significantly higher for the primed group (P = 0.0001 and P = 0.001, respectively). Both HIB conjugate vaccines produce predominantly IgG1 anti-HIB antibody responses. The early response to PRP-OMPC vaccine at 2 months of age may result from adjuvant characteristics of the OMPC.

Preliminary results on the plasma environment of saturn from the pioneer 11 plasma analyzer experiment.

The Ames Research Center Pioneer 11 plasma analyzer experiment provided measurements of the solar wind interaction with Saturn and the character of the plasma environment within Saturn's magnetosphere. It is shown that Saturn has a detached bow shock wave and magnetopause quite similar to those at Earth and Jupiter. The scale size of the interaction region for Saturn is roughly one-third that at Jupiter, but Saturn's magnetosphere is equally responsive to changes in the solar wind dynamic pressure. Saturn's outer magnetosphere is inflated, as evidenced by the observation of large fluxes of corotating plasma. It is postulated that Saturn's magnetosphere may undergo a large expansion when the solar wind pressure is greatly diminished by the presence of Jupiter's extended magnetospheric tail when the two planets are approximately aligned along the same solar radial vector.

Electron observations and ion flows from the pioneer venus orbiter plasma analyzer experiment.

Additional plasma measurements in the vicinity of Venus are presented which show that (i) there are three distinct plasma electron populations-solar wind electrons, ionosheath electrons, and nightside ionosphere electrons; (ii) the plasma ion flow pattern in the ionosheath is consistent with deflected flow around a blunt obstacle; (iii) the plasma ion flow velocities near the downstream wake may, at times, be consistent with the deflection of plasma into the tail, closing the solar wind cavity downstream from Venus at a relatively close distance (within 5 Venus radii) to the planet; (iv) there is a separation between the inner boundary of the downstream ionosheath and the upper boundary of the nightside ionosphere; and (v) during the first 4.5 months in orbit the measured solar wind plasma speed continued to vary, showing a number of high-speed, but generally nonrecurrent, streams.

Pioneer 11 encounter: preliminary results from the ames research center plasma analyzer experiment.

Pioneer 11 observations of the interaction of Jupiter's magnetosphere with the distant solar wind have confirmed the earlier Pioneer 10 observations of the great size and extreme variability of the outer magnetosphere. The nature of the plasma transitions across Jupiter's bow shock and magnetopause as observed on Pioneer 10 have also been confirmed on Pioneer 11. However, the northward direction of the Pioneer 11 outbound trajectory and the distance of the final magnetopause crossing (80 Jupiter radii) now suggest that Jupiter's magnetosphere is extremely broad with a half-thickness (normal to the ecliptic plane in the noon meridian) which is comparable to or greater than the sunward distance to the nose.